共查询到20条相似文献,搜索用时 31 毫秒
1.
Meyer-Schwesinger C Dehde S Klug P Becker JU Mathey S Arefi K Balabanov S Venz S Endlich KH Pekna M Gessner JE Thaiss F Meyer TN 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(6):3218-3229
Subepithelial immune complex deposition in glomerular disease causes local inflammation and proteinuria by podocyte disruption. A rat model of membranous nephropathy, the passive Heymann nephritis, suggests that Abs against specific podocyte Ags cause subepithelial deposit formation and podocyte foot process disruption. In this study, we present a mouse model in which a polyclonal sheep anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia, and elevated cholesterol and triglycerides. Development of proteinuria was biphasic: an initial protein loss was followed by a second massive increase of protein loss beginning at approximately day 10. By histology, podocytes were swollen. Electron microscopy revealed 60-80% podocyte foot process effacement and subepithelial deposits, but no disruption of the glomerular basement membrane. Nephrin and synaptopodin staining was severely disrupted, and podocyte number was reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage. Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the glomerular filtration barrier. Immunoelectron microscopy localized the Ab to podocyte foot processes and the glomerular basement membrane. Similarly, immunohistochemistry localized mouse IgG to the subepithelial space. The third complement component (C3) was detected in a linear staining pattern along the glomerular basement membrane and in the mesangial hinge region. However, C3-deficient mice were not protected from podocyte damage, indicating a complement-independent mechanism. Twenty proteins were identified as possible Ags to the sheep anti-podocyte serum by mass spectrometry. Together, these data establish a reproducible model of immune-mediated podocyte injury in mice with subepithelial immune complex formation. 相似文献
2.
Aunapuu M Roosaar P Järveots T Kurrikoff K Kõks S Vasar E Arend A 《Transgenic research》2008,17(6):1079-1089
Although cholecystokinin is a regulatory peptide with a predominant role in the brain and the gastrointestinal tract, there
is an increasing evidence for its role in the kidney. The aim of this study was to reveal morphological changes in the structure
of kidney of mice with cholecystokinin overexpression by means of light, transmission and scanning electron microscope, and
atomic force microscopy. Using immunohistochemistry the expression of important basement membrane proteins collagen IV, laminin
and fibronectin, as well the distribution of cholecystokinin-8 in the renal structures was evaluated. The altered morphology
of kidneys of mice with cholecystokinin overexpression was seen by all microscopic techniques used. The renal corpuscles were
relatively small with narrow capsular lumen. The basement membranes of renal tubules were thickened and the epithelial cells
were damaged, which was more pronounced for distal tubules. Characteristic feature was the increased number of vesicles seen
throughout the epithelial cells of proximal and especially in distal tubules reflecting to the enhanced cellular degeneration.
The relative expression of laminin but not collagen IV in the glomerular basement membrane was higher than in the tubular
basement membranes. The content of fibronectin, in opposite, was higher in tubular membranes. Cholecystokinin-8 was clearly
expressed in the glomeruli, in Bowman’s capsule, in proximal and distal tubules, and in collecting ducts. Ultrastructural
studies showed irregularly thickened glomerular basement membranes to which elongated cytopodia of differently shaped podocytes
were attached. As foot processes were often fused the number of filtration pores was decreased. In conclusion, cholecystokinin
plays important role in renal structural formation and in functioning as different aspects of urine production in mice with
cholecystokinin overexpression are affected-the uneven glomerular basement membrane thickening, structural changes in podocytes
and in filtration slits affect glomerular filtration, while damaged tubular epithelial cells and changed composition of thickened
tubular basement membranes affect reabsorption. 相似文献
3.
Hurskainen T Moilanen J Sormunen R Franzke CW Soininen R Loeffek S Huilaja L Nuutinen M Bruckner-Tuderman L Autio-Harmainen H Tasanen K 《Cell and tissue research》2012,348(3):579-588
The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration. 相似文献
4.
Rahal S McVeigh LI Zhang Y Guan Y Breyer MD Kennedy CR 《Canadian journal of physiology and pharmacology》2006,84(8-9):877-885
In experimental glomerulonephritis, inhibition of renal prostaglandin (PG) synthesis by nonsteroidal-anti-inflammatory drugs (NSAIDs) moderates proteinuria, yet can induce harmful effects on renal blood flow and Na+ - K+ - water balance thereby implicating 1 or more prostanoid receptor subtypes. We investigated the role of the PGE2 EP1 receptor in nephritis since it is expressed in the glomerulus, collecting duct and vasculature in which its activity might contribute to adaptive or maladaptive responses. Accordingly, a mouse model of accelerated antiglomerular basement membrane (anti-GBM) nephrotoxic serum (NTS) nephritis was induced in mice with targeted-deletion of the EP1 receptor (EP1-/-). Proteinuria was similar between wild-type (wt) and EP1-/- NTS groups, thus negating a role for this subtype in modulating the glomerular permeability barrier in this model of anti-GBM NTS. However, overall renal damage was more acute in NTS EP1-/- mice, as evidenced by the degree of glomerular mesangial matrix expansion and the frequency of tubular dilatations. These changes in renal pathology were accompanied by stronger impairment of renal function in NTS EP1-/- mice, such that levels of serum creatinine, urea, Na+, and K+ were each significantly higher than those observed in NTS wt mice. Lastly, compared with wt mice, induction of NTS more severely reduced urine osmolality and body mass in EP1-/- mice. Taken together, the increased renal impairment seen in NTS EP1-/- mice suggests that the EP1 subtype plays a compensatory role in the context of acute nephritis. 相似文献
5.
Glomerular and tubular basement membranes were isolated from fetal, neonatal, young and adult bovine kidneys.An isolation method with sieves for both glomeruli and tubules from the same kidney was developed. A detergent procedure appeared to give purer glomerular and tubular basement membrane preparations than the generally used sonication method. No large differences were found in the composition of glomerular and tubular basement membrane of adult animals.Glomerular and tubular basement membrane preparations of the four age groups showed an increase with age of hydroxylysine and both 3- and 4-hydroxyproline. The most marked increases appeared at different stages of development, that of tubular basement membrane being between fetal and neonatal stages and glomerular basement membrane between 18 weeks old and adult animals. The ratio of 3- to 4-hydroxyproline increased considerably during development. Total imino acid content was higher for both types of basement membrane from adult than from young animals, while total content of hydroxylysine plus lysine remained fairly constant.The increase in hydroxylation of lysine was accompanied by a corresponding change in glucose and galactose content so that the ratio of galactose to hydroxylysine or glucose to galactose remained constant. Fucose content of both types of basement membranes was the same for all age groups but content of aminosugars and mannose gradually increased with age. 相似文献
6.
R W ten Kate A Zwiers W M Moons J F Slegers A J Donker S G Meuwissen 《Renal physiology and biochemistry》1989,12(1):41-46
Pepsinogen A (PGA) and pepsinogen C (PGC) are low-molecular-weight proteins synthesized by the gastric mucosa. Data in man suggest that both pepsinogens are almost freely filtered through the glomerular basement membrane despite a molecular weight of about 43,000 dalton and a strongly negative charge. This promoted us to investigate the glomerular sieving of PGA and PGC in the isolated rat kidney model by measuring their fractional excretions before and after inhibition of tubular function with sodium iodoacetate. During the control episode fractional excretion of PGA was 40 +/- 0.04% and of PGC 42 +/- 0.04% (mean +/- SEM from 9 experiments). After complete inhibition of tubular function a large increase in fractional excretion was found for both pepsinogens: 87 +/- 0.04% for PGA and 95 +/- 0.09% for PGC. It is concluded that tubular secretion does not contribute to the high fractional excretion of pepsinogens and that both PGA and PGC are almost freely filtered through the glomerular basement membrane. 相似文献
7.
It has been proved that both in bovine and rat serum fibronectin concentration increases with age. While in foetal bovine the serum fibronectin concentration was 77 +/- 5 micrograms/ml, in adult cows the concentration of this protein reached 150.0 +/- 5.5 micrograms/ml. In newborn rats, the corresponding fibronectin concentration in the serum was 227 +/- 25 micrograms/ml as compared to 455 +/- 47 micrograms/ml in adult individuals. On the contrary, a drop in fibronectin concentration was found in the bovine glomerular basement membrane: fibronectin represents 3.8 +/- 0.6% of total protein in the newborn, while in animals older than two months this protein was not detectable. Accordingly, in newborn rats fibronectin represents 5.1 +/- 0.6% of total protein in the glomerular basement membrane and drops dramatically to 0.4 +/- 0.1% after one year of life with no detectable changes thereafter. In the alveolar basement membrane the changes are similar as in the glomerular basement membrane. While in newborn rats this protein represents 13.2 +/- 0.5% of total basement membrane protein, it drops to 3.2 +/- 0.3% after two years of life. 相似文献
8.
Hamelin M Borot-Laloi C Friguet B Bakala H 《Archives of biochemistry and biophysics》2003,411(2):215-222
Accumulation of carboxymethylated proteins (CML-proteins) is taken as a biomarker of glycoxidative stress which is thought to contribute to the age-related impairment in tissue and cell function. To investigate the occurrence and extent of glycoxidative damage with aging in rat kidney, serum and urine, we have prepared a polyclonal antibody against CML-modified bovine serum albumin. We subsequently used it for immunolocalization and in enzyme-linked immunosorbent assays to evaluate CML-protein content. In the serum, CML-protein level was 1.43+/-0.14 pmol CML/micrograms protein at 3 months and significantly increased by 50% from 10 to 27 months (1.50+/-0.14 pmol CML/micrograms protein vs 2.27+/-0.26 pmol CML/micrograms protein), albumin and transferrin being the main modified proteins. In the urine, CML-protein level was 2.50+/-0.14 pmol CML/micrograms protein at 3 months and markedly increased from 10 months (2.99+/-0.24 pmol CML/micrograms protein) to 27 months (3.76+/-0.25 pmol CML/micrograms protein), with albumin as the main excreted modified protein. Immunolocalization of CML-proteins in kidney provided evidence for an age-dependent increased accumulation in extracellular matrices. Intense staining of the glomerular basement membrane (GBM), Bowman's capsule, and the tubular basement membrane was found. Additionally, the CML content for collagen from GBM was 195.85+/-28.95 pmol CML/microgrms OHPro at 3 months and significantly increased from 10 months (187.61+/-21.99 pmol CML/micrograms OHPro) to 27 months (334.55+/-62.21 pmol CML/micrograms OHPro). These data show that circulating CML-protein level in serum and urine and CML accumulation in nephron extracellular matrices with aging are increasing in parallel. The CML-protein measurement in serum and urine may thus be used as an index for the assessment of age-associated glycoxidative kidney damage. 相似文献
9.
Kinnunen AI Sormunen R Elamaa H Seppinen L Miller RT Ninomiya Y Janmey PA Pihlajaniemi T 《The Journal of biological chemistry》2011,286(10):7755-7764
Collagen XVIII is characterized by three variant N termini, an interrupted collagenous domain, and a C-terminal antiangiogenic domain known as endostatin. We studied here the roles of this collagen type and its variant isoforms in the mouse kidney. Collagen XVIII appeared to be in a polarized orientation in the tubular basement membranes (BMs), the endostatin domain embedded in the BM, and the N terminus residing at the BM-fibrillar matrix interface. In the case of the glomerular BM (GBM), collagen XVIII was expressed in different isoforms depending on the side of the GBM. The orientation appeared polarized here, too, both the endothelial promoter 1-derived short variant of collagen XVIII and the epithelial promoter 2-derived longer variants having their C-terminal endostatin domains embedded in the BM and the N termini at the respective BM-cell interfaces. In addition to loosening of the proximal tubular BM structure, the Col18a1(-/-) mice showed effacement of the glomerular podocyte foot processes, and microindentation studies showed changes in the mechanical properties of the glomeruli, the Col18a1(-/-) glomeruli being ~30% softer than the wild-type. Analysis of promoter-specific knockouts (Col18a1(P1/P1) and Col18a1(P2/P2)) indicated that tubular BM loosening is due to a lack of the shortest isoform, whereas the glomerular podocyte effacement was due to a lack of the longer isoforms. We suggest that lack of collagen XVIII may also have disparate effects on kidney function in man, but considering the mild physiological findings in the mutant mice, such effects may manifest themselves only late in life or require other compounding molecular changes. 相似文献
10.
M J Zamlauski-Tucker J E Springate J B Van Liew B Noble L G Feld 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1992,199(1):59-64
This study was undertaken to determine whether hyperfiltration exists at the single nephron level and whether albumin excretion is increased early in the course of diabetes in Biobreeding rats. Diabetic rats were studied at 8-12 weeks after the onset of diabetes. Control animals were age-matched, diabetes-resistant rats. Urinary and tubular fluid albumin concentrations were measured by polyacrylamide gel electrophoresis. Clearance and micropuncture techniques were used to determine whole kidney and single nephron glomerular filtration rate, renal blood flow, and glomerular capillary pressure. The urinary albumin excretion rate (1.3 +/- 0.1 mg/24 hr) and the tubular fluid albumin concentration (4.7 +/- 0.7 mg/dl) in the diabetic group were significantly elevated when compared with urinary albumin excretion (0.9 +/- 0.1 mg/24 hr) and tubular fluid albumin concentration (2.5 +/- 0.5 mg/dl) in the control group. There were no significant differences in glomerular hemodynamics (whole kidney or single nephron glomerular filtration rate or glomerular capillary pressure) between diabetic and control rats. The kidney weight and kidney weight to body weight ratio were significantly higher in diabetic rats when compared with control rats. Early diabetes in Biobreeding rats is characterized by mild albuminuria and increased kidney size, but not glomerular hyperfiltration. 相似文献
11.
Xiaodong Zhu Zhaohong Chen Caihong Zeng Ling Wang Feng Xu Qing Hou Zhihong Liu 《Journal of morphology》2016,277(8):1104-1112
The zebrafish pronephros is a valuable model for studying kidney development and diseases. Ultrastructural studies have revealed that zebrafish and mammals share similarities in nephron structures such as podocytes, slit diaphragms, glomerular basement membrane, and endothelium. However, the basic ultrastructural features of the pronephric glomerulus during glomerulogenesis have not been characterized. To understand these features, it is instructive to consider the developmental process of the pronephros glomerulus. Here, we describe the ultrastructural features of pronephric glomerulus in detail from 24 h hours post‐fertilization (hpf) to 144 hpf, the period during which the pronephric glomerulus develops from initiation to its mature morphology. The pronephric glomerulus underwent progressive morphogenesis from 24 to 72 hpf, and presumptive glomerular cells were observed ventral to the aorta region at 24 hpf. The nascent glomerular basement membrane and initial lumen were formed at 36 hpf. A lumen was clearly visible in the region of the pronephros at 48 hpf. At 60 hpf, the pronephric glomerulus contained more patches of capillaries. After these transformations, the complex capillary vessel networks had formed inside the glomerulus, which was surrounded by podocyte bodies with elaborate foot processes as well as well‐formed glomerular basement membrane by 72 hpf. The number of renal glomerular cells rapidly increased, and the glomerulus presented its delicate structural features by 96 hpf. Morphogenesis was completed at 120 hpf with the final formation of the pronephric glomerulus. J. Morphol. 277:1104–1112, 2016. © 2016 Wiley Periodicals, Inc. 相似文献
12.
Increased susceptibility of decay-accelerating factor deficient mice to anti-glomerular basement membrane glomerulonephritis 总被引:8,自引:0,他引:8
Sogabe H Nangaku M Ishibashi Y Wada T Fujita T Sun X Miwa T Madaio MP Song WC 《Journal of immunology (Baltimore, Md. : 1950)》2001,167(5):2791-2797
To prevent complement-mediated autologous tissue damage, host cells express a number of membrane-bound complement inhibitors. Decay-accelerating factor (DAF, CD55) is a GPI-linked membrane complement regulator that is widely expressed in mammalian tissues including the kidney. DAF inhibits the C3 convertase of both the classical and alternative pathways. Although DAF deficiency contributes to the human hematological syndrome paroxysmal nocturnal hemoglobinuria, the relevance of DAF in autoimmune tissue damage such as immune glomerulonephritis remains to be determined. In this study, we have investigated the susceptibility of knockout mice that are deficient in GPI-anchored DAF to nephrotoxic serum nephritis. Injection of a subnephritogenic dose of rabbit anti-mouse glomerular basement membrane serum induced glomerular disease in DAF knockout mice but not in wild-type controls. When examined at 8 days after anti-glomerular basement membrane treatment, DAF knockout mice had a much higher percentage of diseased glomeruli than wild-type mice (68.8 +/- 25.0 vs 10.0 +/- 3.5%; p < 0.01). Morphologically, DAF knockout mice displayed increased glomerular volume (516 +/- 68 vs 325 +/- 18 x 10(3) microm(3) per glomerulus; p < 0.0001) and cellularity (47.1 +/- 8.9 vs 32.0 +/- 3.1 cells per glomerulus; p < 0.01). Although the blood urea nitrogen level showed no difference between the two groups, proteinuria was observed in the knockout mice but not in the wild-type mice (1.4 +/- 0.7 vs 0.02 +/- 0.01 mg/24 h albumin excretion). The morphological and functional abnormalities in the knockout mouse kidney were associated with evidence of increased complement activation in the glomeruli. These results support the conclusion that membrane C3 convertase inhibitors like DAF play a protective role in complement-mediated immune glomerular damage in vivo. 相似文献
13.
An electron microscope study of kidney basement membrane changes in the mouse by lipoteichoic acid from Streptococcus pyogenes 总被引:4,自引:0,他引:4
Mice injected repeatedly, intraperitoneally or intravenously, for approximately 1 month with a total of 1.04 mg lipoteichoic acid from a nephritogenic strain of Streptococcus pyogenes lost weight. Analysis by electron microscopy revealed that they also exhibited extensive kidney changes in basement membrane morphology which resembled, in part, those observed in human poststreptococcal glomerulonephritis. For example, the glomerular basement membrane became electron dense and exhibited at least a twofold increase in width sporadically within the same preparation after exposure to lipoteichoic acid. Also, whereas appreciable loss or reduction in epithelial foot processes as a result of fusion was clearly evident, epithelial slits and slit membranes or diaphragms between normal foot processes were not selectively affected. In addition, another mostly thickened, highly coiled or serpentinelike basement membrane with amorphous nodules appeared in these preparations. This type membrane was not observed surrounding the capillary lumina and was the most pronounced abnormality apparent in almost all preparations from mice exposed to lipoteichoic acid. Likewise, the proximal tubular basement membrane became variable in width and increased in electron density in mice given lipoteichoic acid as compared with controls. In addition, this membrane was often punctuated with various morphological protrusions originating from only its thickened areas and which extended away from, and not into, the capillary space. This change was only associated with the basement membrane of the proximal tubular capillaries. All membrane changes persisted but gradually subsided, with normal kidney membrane morphology reappearing on the 4th day following the last injection of lipoteichoic acid.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
14.
S. P. Gambaryan 《Journal of fish biology》1988,33(3):383-398
The anatomy and ultrastructure of nephrons were studied in various euryhaline and freshwater sturgeons. Microdissection failed to reveal marked differences in the nephron structure between freshwater and euryhaline fishes which might be considered as specific adaptations to the salinity of the environment. Some adaptive changes in the nephron structure were revealed by electron microscopic examination. The glomerular basal membrane is thicker in euryhaline sturgeons than in the freshwater sterlet. The processes of mesangial cells penetrating the basal membrane are much more numerous in fishes caught in the sea than in those from fresh water. Euryhaline sturgeons exhibit a great variability in the ultrastructure of epithelial cells of proximal and distal tubules. The number of mitochondria-rich cells possessing well-developed basolateral foldings is significantly higher in fishes caught in the sea. In the freshwater sterlet the ultrastructure of the epithelium of proximal and distal tubules resembles that in freshwater teleosts.
Comparison was made of the kidney morphology and ultrastructure in sturgeons, elasmo branchs and bony fishes. It is speculated that in sturgeons the adaptation to varying salinity is achieved by changes in the ultrastructure of glomeruli and differentiation of the cells of the tubular epithelium. 相似文献
Comparison was made of the kidney morphology and ultrastructure in sturgeons, elasmo branchs and bony fishes. It is speculated that in sturgeons the adaptation to varying salinity is achieved by changes in the ultrastructure of glomeruli and differentiation of the cells of the tubular epithelium. 相似文献
15.
M Cheignon H Bakala S Cornet R Djaziri J Schaeverbeke 《Biology of the cell / under the auspices of the European Cell Biology Organization》1987,60(1):49-56
The distribution of basement membrane glycoproteins (type IV collagen, laminin, fibronectin, and proteoglycans) was studied in foetal rat kidney by immunohistochemical techniques using polyclonal antibodies. From the first stages of nephron differentiation, all these glycoproteins were detectable by immunofluorescence in the tubular and glomerular basement membranes and in the mesangial matrix. As differentiation proceeded, labelling of glycoproteins progressively intensified, except for that of fibronectin, which gradually decreased in the glomerular basement membrane (GBM) and was barely observable at full differentiation. With immunoperoxidase staining in electron microscopy, all glycoproteins were seen to be widely dispersed in the spaces between the epithelial and endothelial glomerular cells so long as the GBM remained a loose structure. However, after it became a compact, 3-layered formation, type IV collagen and laminin were distributed throughout the GBM, whereas proteoglycans and anionic sites appeared as 2 rows of granules confined to the laminae rarae. 相似文献
16.
Pozzi A Jarad G Moeckel GW Coffa S Zhang X Gewin L Eremina V Hudson BG Borza DB Harris RC Holzman LB Phillips CL Fassler R Quaggin SE Miner JH Zent R 《Developmental biology》2008,316(2):288-301
Integrins are transmembrane heteromeric receptors that mediate interactions between cells and extracellular matrix (ECM). β1, the most abundantly expressed integrin subunit, binds at least 12 α subunits. β1 containing integrins are highly expressed in the glomerulus of the kidney; however their role in glomerular morphogenesis and maintenance of glomerular filtration barrier integrity is poorly understood. To study these questions we selectively deleted β1 integrin in the podocyte by crossing β1flox/flox mice with podocyte specific podocin-cre mice (pod-Cre), which express cre at the time of glomerular capillary formation. We demonstrate that podocyte abnormalities are visualized during glomerulogenesis of the pod-Cre;β1flox/flox mice and proteinuria is present at birth, despite a grossly normal glomerular basement membrane. Following the advent of glomerular filtration there is progressive podocyte loss and the mice develop capillary loop and mesangium degeneration with little evidence of glomerulosclerosis. By 3 weeks of age the mice develop severe end stage renal failure characterized by both tubulointerstitial and glomerular pathology. Thus, expression of β1 containing integrins by the podocyte is critical for maintaining the structural integrity of the glomerulus. 相似文献
17.
Kanasaki K Kanda Y Palmsten K Tanjore H Lee SB Lebleu VS Gattone VH Kalluri R 《Developmental biology》2008,313(2):584-593
The human kidneys filter 180 l of blood every day via about 2.5 million glomeruli. The three layers of the glomerular filtration apparatus consist of fenestrated endothelium, specialized extracellular matrix known as the glomerular basement membrane (GBM) and the podocyte foot processes with their modified adherens junctions known as the slit diaphragm (SD). In this study we explored the contribution of podocyte β1 integrin signaling for normal glomerular function. Mice with podocyte specific deletion of integrin β1 (podocin-Cre β1-fl/fl mice) are born normal but cannot complete postnatal renal development. They exhibit detectable proteinuria on day 1 and die within a week. The kidneys of podocin-Cre β1-fl/fl mice exhibit normal glomerular endothelium but show severe GBM defects with multilaminations and splitting including podocyte foot process effacement. The integrin linked kinase (ILK) is a downstream mediator of integrin β1 activity in epithelial cells. To further explore whether integrin β1-mediated signaling facilitates proper glomerular filtration, we generated mice deficient of ILK in the podocytes (podocin-Cre ILK-fl/fl mice). These mice develop normally but exhibit postnatal proteinuria at birth and die within 15 weeks of age due to renal failure. Collectively, our studies demonstrate that podocyte β1 integrin and ILK signaling is critical for postnatal development and function of the glomerular filtration apparatus. 相似文献
18.
Wen Chih Chiang Chun Fu Lai Chi Ting Su Wei Hao Peng Ching Fang Wu Fan Chi Chang Yi Ting Chen Shuei Liong Lin Yung Ming Chen Kwan Dun Wu Kuo Shyan Lu Tun Jun Tsai 《PloS one》2013,8(12)
Glomerular capillary remodeling is an essential process in the development of glomerular hypertrophy. Angiopoietins, which are important regulators in angiogenesis, plays a role in the development of glomerulus during embryogenesis. Here, we evaluated the influence of angiopoietin on glomerular components and hypertrophy after uninephrectomy in adult male BALB/c mice. The actions of angiopoietin 1 or 2 were systemically antagonized by the subcutaneous administration of antagonists. We observed that the angiopoietin system was activated after uninephrectomy, and that the blockade of angiopoietin 1 or 2 decreased the activation of the angiopoietin receptor—tyrosine kinase with Ig and EGF homology domains-2—and attenuated the development of glomerular and podocyte hypertrophy. The increase in endothelial density staining (anti-CD31) following uninephrectomy was also reversed by angiopoietin 1 or 2 blockades. Glomerular basement thickness and foot process width were observed to decrease in the angiopoietin blockade groups. These changes were associated with the down regulation of the expression of genes for the glomerular matrix and basement membrane, including collagen type IV α1, collagen type IV α2, collagen type IV α5, and laminin α5. Thus, angiopoietin 1 or 2 may play an important role in the development of glomerular hypertrophy after uninephrectomy. A blockade of the angiopoietin system not only influenced the endothelium but also the podocyte, leading to diminished gene expression and morphological changes after uninephrectomy. 相似文献
19.
Weisong Qin Zhongxiu Xu Yizhou Lu Caihong Zeng Chunxia Zheng Shengyu Wang Zhihong Liu 《PloS one》2012,7(9)
To investigate the injury effects of organic solvents on kidney, an animal model of Sprague-Dawley (SD) rats treated with mixed organic solvents via inhalation was generated and characterized. The mixed organic solvents consisted of gasoline, dimethylbenzene and formaldehyde (GDF) in the ratio of 2∶2:1, and were used at 12,000 PPM to treat the rats twice a day, each for 3 hours. Proteinuria appeared in the rats after exposure for 5–6 weeks. The incidences of proteinuria in male and female rats after exposure for 12 weeks were 43.8% (7/16) and 25% (4/16), respectively. Urinary N-Acetyl-β-(D)-Glucosaminidase (NAG) activity was increased significantly after exposure for 4 weeks. Histological examination revealed remarkable injuries in the proximal renal tubules, including tubular epithelial cell detachment, cloud swelling and vacuole formation in the proximal tubular cells, as well as proliferation of parietal epithelium and tubular reflux in glomeruli. Ultrastructural examination found that brush border and cytoplasm of tubular epithelial cell were dropped, that tubular epithelial cells were partially disintegrated, and that the mitochondria of tubular epithelial cells were degenerated and lost. In addition to tubular lesions, glomerular damages were also observed, including segmental foot process fusion and loss of foot process covering on glomerular basement membrane (GBM). Immunofluorescence staining indicated that the expression of nephrin and podocin were both decreased after exposure of GDF. In contrast, increased expression of desmin, a marker of podocyte injury, was found in some areas of a glomerulus. TUNEL staining showed that GDF induced apoptosis in tubular cells and glomerular cells. These studies demonstrate that GDF can induce both severe proximal tubular damage and podocyte injury in rats, and the tubular lesions appear earlier than that of glomeruli. 相似文献
20.
Samy L Habib 《Cell cycle (Georgetown, Tex.)》2018,17(14):1683-1687
One of the first structural changes in diabetic nephropathy (DN) is the renal enlargement. These changes resulted in renal hypertrophy in both glomerular and tubular cells. Shrink in the kidney size, which described as kidney atrophy resulted from the loss of nephrons or abnormal nephron function and lead to loss of the kidney function. On the other hand, increase in kidney size, which described as hypertrophy resulted from increase in proximal tubular epithelial and glomerular cells size. However overtime, tubular atrophy and tubulointerstitial fibrosis occurs as subsequent changes in tubular cell hypertrophy, which is associated with the infiltration of fibroblast cells into the tubulointerstitial space. The rate of deterioration of kidney function shows a strong correlation with the degree of tubulointerstitial fibrosis. A consequence of long-standing diabetes/hyperglycemia may lead to major changes in renal structure that occur but not specific only to nephropathy. Identifying type of cells that involves in renal atrophy and hypertrophy may help to find a therapeutic target to treat diabetic nephropathy. In summary, the early changes in diabetic kidney are mainly includes the increase in tubular basement membrane thickening which lead to renal hypertrophy. On the other hand, only renal tubule is subjected to apoptosis, which is one of the characteristic morphologic changes in diabetic kidney to form tubular atrophy at the late stage of diabetes. 相似文献