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1.
Pei Y 《Trends in molecular medicine》2001,7(4):151-156
An intriguing feature of autosomal dominant polycystic kidney disease (ADPKD) is the focal and sporadic nature of individual cyst formation. Typically, only a few renal cysts are detectable in an affected individual during the first two decades of life. By the fifth decade, however, hundreds to thousands of renal cysts can be found in most patients. Additionally, significant intra-familial variability of ADPKD has been well documented. Taken together, these findings suggest that factor(s) in addition to the germline mutation of a polycystic kidney disease gene might be required for individual cyst formation. Indeed, recent studies have provided compelling evidence in support of a "two-hit" model of cystogenesis in ADPKD. In this model, inactivation of both copies of a polycystic kidney disease gene by germline and somatic mutations within an epithelial cell provides growth advantages for it to proliferate clonally into a cyst. This article highlights key findings of these recent studies and discusses the controversies and implications of the "two-hit" model in ADPKD. 相似文献
2.
Blazer-Yost BL Blacklock BJ Flaig S Bacallao RL Gattone VH 《Cellular physiology and biochemistry》2011,28(6):1255-1264
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the slow growth of multiple fluid-filled cysts predominately in the kidney tubules and liver bile ducts. Elucidation of mechanisms that control cyst growth will provide the basis for rational therapeutic intervention. We used electrophysiological methods to identify lysophosphatidic acid (LPA) as a component of cyst fluid and serum that stimulates secretory Cl- transport in the epithelial cell type that lines renal cysts. LPA effects are manifested through receptors located on the basolateral membrane of the epithelial cells resulting in stimulation of channel activity in the apical membrane. Concentrations of LPA measured in human ADPKD cyst fluid and in normal serum are sufficient to maximally stimulate ion transport. Thus, cyst fluid seepage and/or leakage of vascular LPA into the interstitial space are capable of stimulating epithelial cell secretion resulting in cyst enlargement. These observations are particularly relevant to the rapid decline in renal function in late-stage disease and to the "third hit" hypothesis that renal injury exacerbates cyst growth. 相似文献
3.
Autosomal dominant polycystic kidney disease (ADPKD) is a common genetic disorder characterized by the formation of fluid-filled cysts in the kidney and progressive renal failure. Other manifestations of ADPKD include the formation of cysts in other organs (liver, pancreas, and spleen), hypertension, cardiac defects, and cerebral aneurysms. The loss of function of the polycystin -1 and -2 results in the formation of epithelium-lined cysts, a process that depends on initial epithelial proliferation. cDNA microarrays powerfully monitor gene expression and have led to the discoveries of pathways regulating complex biological processes. We undertook to profile the gene expression patterns of epithelial cells derived from the cysts of ADPKD patients using the cDNA microarray technique. Candidate genes that were differently expressed in cyst tissues were identified. 19 genes were up-regulated, and 6 down-regulated. Semi-quantitative RT-PCR results were consistent with the microarray findings. To distinguish between normal and epithelial cells, we used the hierarchical method. The results obtained may provide a molecular basis for understanding the biological meaning of cytogenesis. 相似文献
4.
Yook YJ Yoo KH Song SA Seo MJ Ko JY Kim BH Lee EJ Chang E Woo YM Park JH 《BMB reports》2012,45(3):189-193
Cyst formation is a major characteristic of ADPKD and is caused by the abnormal proliferation of epithelial cells. Renal cyst formation disrupts renal function and induces diverse complications. The mechanism of cyst formation is unclear. mIMCD-3 cells were established to develop simple epithelial cell cysts in 3-D culture. We confirmed previously that Mxi1 plays a role in cyst formation in Mxi1-deficient mice. Cysts in Mxi1 transfectanted cells were showed by collagen or mebiol gels in 3-D cell culture system. Causative genes of ADPKD were measured by q RT-PCR. Herein, Mxi1 transfectants rarely formed a simple epithelial cyst and induced cell death. Overexpression of Mxi1 resulted in a decrease in the PKD1, PKD2 and c-myc mRNA relating to the pathway of cyst formation. These data indicate that Mxi1 influences cyst formation of mIMCD-3 cells in 3-D culture and that Mxi1 may control the mechanism of renal cyst formation. [BMB reports 2012; 45(3): 189-193]. 相似文献
5.
In autosomal dominant polycystic kidney disease (ADPKD), the inexorable growth of numerous fluid-filled cysts leads to massively enlarged kidneys, renal interstitial damage, inflammation, and fibrosis, and progressive decline in kidney function. It has long been recognized that interstitial fibrosis is the most important manifestation associated with end-stage renal disease; however, the role of abnormal extracellular matrix (ECM) production on ADPKD pathogenesis is not fully understood. Early evidence showed that cysts in end-stage human ADPKD kidneys had thickened and extensively laminated cellular basement membranes, and abnormal regulation of gene expression of several basement membrane components, including collagens, laminins, and proteoglycans by cyst epithelial cells. These basement membrane changes were also observed in dilated tubules and small cysts of early ADPKD kidneys, indicating that ECM alterations were early features of cyst development. Renal cystic cells were also found to overexpress several integrins and their ligands, including ECM structural components and soluble matricellular proteins. ECM ligands binding to integrins stimulate focal adhesion formation and can promote cell attachment and migration. Abnormal expression of laminin-332 (laminin-5) and its receptor α6β4 stimulated cyst epithelial cell proliferation; and mice that lacked laminin α5, a component of laminin-511 normally expressed by renal tubules, had an overexpression of laminin-332 that was associated with renal cyst formation. Periostin, a matricellular protein that binds αVβ3- and αVβ5-integrins, was found to be highly overexpressed in the kidneys of ADPKD and autosomal recessive PKD patients, and several rodent models of PKD. αVβ3-integrin is also overexpressed by cystic epithelial cells, and the binding of periostin to αVβ3-integrin activates the integrin-linked kinase and downstream signal transduction pathways involved in tissue repair promoting cyst growth, ECM synthesis, and tissue fibrosis. This chapter reviews the roles of the ECM, integrins, and focal adhesion signaling in cyst growth and fibrosis in PKD. 相似文献
6.
Autosomal dominant polycystic kidney disease (ADPKD) is a progressive chronic kidney disease. To date there are no effective medicines to halt development and growth of cysts. In the present study, we explored novel effects of celecoxib (CXB), a COX-2 specific inhibitor, on primary cultures of human ADPKD cyst-lining epithelial cells. Primary cultures of ADPKD cyst-lining epithelial cells were obtained from five patients. Effects of CXB were measured by various assays to detect BrdU incorporation, apoptosis and proliferation in vitro. Additionally, effects of CXB on kidney weight, the cyst index, the fibrosis index, blood urea nitrogen (BUN), serum creatinine (SCr), serum 6-keto-PGF-1α, serum thromboxane-2 (TXB2) and renal PCNA expression were assessed in Han:SPRD rat, a well-characterized rodent model of PKD. CXB inhibited proliferation of ADPKD cyst-lining epithelial cells, blocked the release of VEGF from the cells and induced extensive apoptosis in a time- and dose-dependent manner. Moreover, CXB up-regulated the cell cycle negative regulator p21(CIP/WAF1) and the cell cycle positive regulator Cyclin A, blocked ERK1/2 phosphorylation, induced apoptotic factors (Bax and caspase-3) and reduced Bcl-2. Furthermore, CXB inhibited the expression of VEGFR-2 and Raf-1 in ADPKD cyst-lining epithelial cells. CXB markedly reduced the cyst index, the fibrosis index, leukocyte infiltration, BUN, SCr, serum 6-keto-PGF-1α, TXB2 and renal PCNA expression in Han:SPRD rat. We demonstrated for the first time that CXB could suppress renal cyst-lining growth both in vitro and in vivo in Han:SPRD rat. CXB can inhibit proliferation, suppress cell cycle progression, and induce apoptosis in ADPKD cyst-lining epithelial cells through the inhibition of the VEGF/VEGFR-2/Raf-1/MAPK/ERK signaling pathway. 相似文献
7.
Background: Lymphangioma of the pancreas is an extremely rare benign tumour of lymphatic origin, with only four cases diagnosed by EUS‐FNA reported to date. Methods and materials: Five cases of either cytologically or histologically diagnosed pancreatic lymphangioma with pre‐operative cytological analysis by EUS‐FNAC were reviewed. Results: All patients were female, with a mean age of 56.4 years. By imaging, the cystic lesions ranged in size from 2 to 7 cm (mean 4.5 cm) and were mainly located in the head of the pancreas. All cysts had thin walls and no cyst demonstrated a mural nodule. Diagnosis based on imaging features was benign in all cases due to the absence of high‐risk features. Four samples were sent for biochemical analysis, which showed low CEA levels (range, <0.5–19.4 ng/ml; mean, 5.45 ng/ml) and CA 19.9 and CA 72.4 levels within normal range. All cyst fluids showed numerous small lymphocytes with no atypia; no epithelial cells were present, including no gastrointestinal contamination. Flow cytometry in two cases showed T lymphocytes with a mature phenotype. Surgical resection in two patients confirmed the cytological diagnosis. Benign clinical follow‐up was available in three patients at 2, 3 and 3.5 years. Conclusion: A multimodal approach to cytological diagnosis (combining clinical, radiological and cyst fluid gross, biochemical and cytological characteristics) can lead to the diagnosis of this cystic neoplasm and distinguish it from other more common cysts in the pancreas, potentially avoiding the need for unnecessary surgery. 相似文献
8.
Identification of a locus for autosomal dominant polycystic liver disease, on chromosome 19p13.2-13.1
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Reynolds DM Falk CT Li A King BF Kamath PS Huston J Shub C Iglesias DM Martin RS Pirson Y Torres VE Somlo S 《American journal of human genetics》2000,67(6):1598-1604
Polycystic liver disease (PCLD) is characterized by the growth of fluid-filled cysts of biliary epithelial origin in the liver. Although the disease is often asymptomatic, it can, when severe, lead to complications requiring surgical therapy. PCLD is most often associated with autosomal dominant polycystic kidney disease (ADPKD); however, families with an isolated polycystic liver phenotype without kidney involvement have been described. The clinical presentation and histological features of polycystic liver disease in the presence or absence of ADPKD are indistinguishable, raising the possibility that the pathogenetic mechanisms in the diseases are interrelated. We ascertained two large families with polycystic liver disease without kidney cysts and performed a genomewide scan for genetic linkage. A causative gene, PCLD, was mapped to chromosome 19p13.2-13.1, with a maximum LOD score of 10.3. Haplotype analysis refined the PCLD interval to 12.5 cM flanked by D19S586/D19S583 and D19S593/D19S579. The discovery of genetic linkage will facilitate diagnosis and study of this underdiagnosed disease entity. Identification of PCLD will be instrumental to an understanding of the pathogenesis of cyst formation in the liver in isolated PCLD and in ADPKD. 相似文献
9.
Kher R Sha EC Escobar MR Andreoli EM Wang P Xu WM Wandinger-Ness A Bacallao RL 《American journal of physiology. Cell physiology》2011,301(1):C99-C105
While a variety of genetic mutations have been shown to be associated with renal cyst formation, mechanisms of renal cyst formation are largely unknown. In prior communications we described alterations in E-cadherin assembly in cultured cystic epithelial cells (Charron AJ, Nakamura S, Bacallao R, Wandinger-Ness A. J Cell Biol 149: 111-124, 2000). Using the same cell line we assayed cadherin expression by RT-PCR using primer pairs that anneal to highly conserved sequences of cadherin genes but flank informative regions of cadherins. Using this approach we found that autosomal dominant polycystic kidney disease (ADPKD) cells express cadherin 8, a neuronal cadherin with limited expression in the kidney. Immunohistochemistry confirmed cadherin 8 expression in cystic epithelia. To test the functional significance of cadherin 8 expression in renal epithelial cells, we adapted a three-dimensional collagen culture method in which HK-2 cells form tubule structures and microinjected adenovirus into the matrix space surrounding tubule structures. Adenovirus expressing cadherin 8 under the control of a tet promoter caused cyst structures to grow out of the tubules when coinjected with adenovirus expressing a tet transactivator. Microinjection of single adenovirus expressing either tet transactivator or cadherin 8 failed to cause cyst formation. When doxycycline was added to the culture, following coinjection of adenovirus, there was a dose-response reduction in cadherin 8 expression and cyst formation. Similarly, HK-2 cells transfected with Flag-tagged cadherin 8 form cysts in addition to tubular structures. HK-2 cells transfected with Flag-tagged N-cadherin do not form cysts. These data suggest that ectopic expression of cadherin 8 in renal epithelial cells is sufficient to cause the morphogenic pattern of cyst formation. 相似文献
10.
11.
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by cyst formation initiated by dedifferentiation and
proliferation of renal tubular epithelial cells. Renal tubular epithelial cells (RTC, derived from normal kidney tissue) in
primary cultures exhibit both homogeneous expression of γ-glutamyl transferase and low molecular weight cytokeratin, two different
markers for proximal and distal renal epithelial cells, respectively. RTC in cultures also abnormally express the dedifferentiation
markers vimentin and PAX-2, which are proteins normally expressed in epithelial cells lining cysts in ADPKD kidneys but not
tubular cells in normal kidneys. In contrast, different cultures of cystic epithelial cells (CEC, derived from the cysts walls
of polycystic kidneys) display variable expression of cytokeratin, γ-glutamyl transferase, and PAX-2, but a constant level
of vimentin. Importantly, RTC and CEC exhibit the capacity to convert to their respective original structures by forming tubules
and cysts, respectively, when cultured in a three-dimensional gel matrix, whereas HK-2, LLC-PK1, and MDCK renal epithelial
cell lines form cell aggregates or cysts. Our study demonstrates that the marker expression of the various epithelial cell
types is not highly stable in primary cultures. Their modulation is different in cells originating from normal and ADPKD kidneys
and in cells cultured in monolayer and three-dimensions. These results indicate the plasticity of epithelial cells that display
a mixed epithelial/dedifferentiated/mesenchymal phenotype during their expansion in culture. However, RTC and CEC morphogenic
epithelial properties in three-dimensional cultures are similar to those in vivo. Thus, this model is useful for studying
the mechanisms leading to tubulogenesis and cystogenesis.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.
This work was supported by a grant from The Polycystic Kidney Foundation. We gratefully acknowledge the support of the Children’s
Medical Research Institute and Children’s Miracle Network Foundation. 相似文献
12.
Pey R Bach J Schieren G Gretz N Hafner M 《In vitro cellular & developmental biology. Animal》1999,35(10):571-579
Summary Autosomal dominant polycystic kidney disease (ADPKD) is one of the most frequent human inherited diseases. The main feature
of the disease is the development of renal cysts, first occurring in the proximal tubules, and with time, dominating all segments
of the nephron, leading to end-stage renal disease in 50% of the patients in their fifth decade of life. A therapy for polycystic
kidney disease (PKD) has not yet been developed. Patients coming to end-stage ADPKD require long-term dialysis and/or transplantation.
A suitable animal model to study ADPKD is the spontaneously mutated Han:SPRD (cy/ +) rat, but a method to cultivate Han:SPRD (cy/ +) derived renal cells which preserves their ability to form cyst-like structures in vitro has previously not been reported.
Based on this well-characterized animal model, we developed a cell culture model of renal cyst formation in vitro. When renal
cells of the Han:SPRD (cy/ +) rat were isolated and cultured under conditions that prevent cell-substratum adhesion, large amounts of cyst-like structures
were formed de novo from Han:SPRD (cy/ +) derived renal cells, but only a few from control rat renal cells. In contrast, when cultivated on plastic as monolayer
cultures, Han:SPRD (cy/ +)-derived and control rat-derived renal cells were indistinguishable and did not form cyst-like structures. Immunohistochemical
characterization of the cyst-like structures suggests tubular epithelial origin of the cyst-forming cells. The amount of cysts
formed from Han:SPRD (cy/ +)-derived renal cells grown in a stationary suspension culture is susceptible to modulation by different conditions. Human
cyst fluid and epidermal growth factor both stimulated the formation of cysts from Han:SPRD (cy/ +)-derived renal cells whereas taxol inhibited cystogenesis. In contrast, neither human cyst fluid nor epidermal growth
factor affected the amount of cysts formed by control rat renal cells. As the culture model reported here allows not only
the distinction of PKD-derived tubular epithelium from its normal counterpart, but also the modulation of cyst formation especially
by Han:SPRD (cy/ +)-derived renal cells, it might be a useful prescreening protocol for potential treatments for PKD and thus reduce the
need for animal experiments.
Both authors contributed equally to the work. 相似文献
13.
《Cell cycle (Georgetown, Tex.)》2013,12(11):1550-1554
Tubular epithelial cell apoptosis occurs in most animal models of polycystic kidney disease (PKD) and in kidneys from humans with autosomal dominant polycystic kidney disease (ADPKD). Induction of apoptosis in cultured tubular epithelial cells results in cyst formation. Induction of apoptosis in the kidney in Bcl-2 deficient mice results in increased proliferation of tubular epithelium and cyst formation. Caspase inhibition reduces tubular apoptosis and proliferation and slows disease progression in the Han:SPRD rat model of PKD. Thus, there is evidence that both epithelial cell apoptosis and proliferation are dysregulated in ADPKD and may represent a general mechanism for cyst growth. 相似文献
14.
《Trends in molecular medicine》2023,29(4):268-281
Autosomal dominant polycystic kidney disease (ADPKD) is a life-threatening monogenic disease caused by mutations in PKD1 and PKD2 that encode polycystin 1 (PC1) and polycystin 2 (PC2). PC1/2 localize to cilia of renal epithelial cells, and their function is believed to embody an inhibitory activity that suppresses the cilia-dependent cyst activation (CDCA) signal. Consequently, PC deficiency results in activation of CDCA and stimulates cyst growth. Recently, re-expression of PCs in established cysts has been shown to reverse PKD. Thus, the mode of action of PCs resembles a ‘counterbalance in cruise control’ to maintain lumen diameter within a designated range. Herein we review recent studies that point to novel arenas for future PC research with therapeutic potential for ADPKD. 相似文献
15.
Autosomal dominant polycystic kidney disease (ADPKD) is the most common inherited cause of kidney failure and characterized by the formation of multiple fluid-filled cysts in the kidneys. It is believed that environmental factors may play an important role in the disease progression. However, the molecular identity of autocrine/paracrine factors influencing cyst formation is largely unknown. In this study, we identified transforming growth factor-β2 (TGF-β2) secreted by normal human kidney (NHK) and ADPKD cells as an inhibitor of cystogenesis in 3D culture system using ADPKD cells from human kidneys. TGF-β2 was identified in conditioned media (CM) of NHK and ADPKD cells as a latent factor activated by heat in vitro. While all TGF-β isoforms recombinant proteins (TGF-β1, -β2, or -β3) displayed a similar inhibitory effect on cyst formation, TGF-β2 was the predominant isoform detected in CM. The involvement of TGF-β2 in the suppression of cyst formation was demonstrated by using a TGF-β2 specific blocking antibody and a TGF-β receptor I kinase inhibitor. TGF-β2 inhibited cyst formation by a mechanism other than activation of p38 mitogen-activated protein (MAP) kinase that mediated cell death in ADPKD cells. Further, we found that TGF-β2 modulated expression of various genes involved in cell-cell and cell-matrix interactions and extracellular matrix proteins that may play a role in the regulation of cystogenesis. Collectively, our results suggest that TGF-β2 secreted by renal epithelial cells may be an inhibitor of cystogenesis influencing the progression of ADPKD. 相似文献
16.
Abeda Jamadar Sreenath M. Suma Sijo Mathew Timothy A. Fields Darren P. Wallace James P. Calvet Reena Rao 《Cell death & disease》2021,12(10)
Autosomal-dominant polycystic kidney disease (ADPKD) is the most common inherited kidney disease and is characterized by progressive growth of fluid-filled cysts. Growth factors binding to receptor tyrosine kinases (RTKs) stimulate cell proliferation and cyst growth in PKD. Nintedanib, a triple RTK inhibitor, targets the vascular endothelial growth-factor receptor (VEGFR), platelet-derived growth-factor receptor (PDGFR), and fibroblast growth-factor receptor (FGFR), and is an approved drug for the treatment of non-small-cell lung carcinoma and idiopathic lung fibrosis. To determine if RTK inhibition using nintedanib can slow ADPKD progression, we tested its effect on human ADPKD renal cyst epithelial cells and myofibroblasts in vitro, and on Pkd1f/fPkhd1Cre and Pkd1RC/RC, orthologous mouse models of ADPKD. Nintedanib significantly inhibited cell proliferation and in vitro cyst growth of human ADPKD renal cyst epithelial cells, and cell viability and migration of human ADPKD renal myofibroblasts. Consistently, nintedanib treatment significantly reduced kidney-to-body-weight ratio, renal cystic index, cystic epithelial cell proliferation, and blood-urea nitrogen levels in both the Pkd1f/fPkhd1Cre and Pkd1RC/RC mice. There was a corresponding reduction in ERK, AKT, STAT3, and mTOR activity and expression of proproliferative factors, including Yes-associated protein (YAP), c-Myc, and Cyclin D1. Nintedanib treatment significantly reduced fibrosis in Pkd1RC/RC mice, but did not affect renal fibrosis in Pkd1f/fPkhd1Cre mice. Overall, these results suggest that nintedanib may be repurposed to effectively slow cyst growth in ADPKD.Subject terms: Growth factor signalling, Polycystic kidney disease 相似文献
17.
Polycystins, calcium signaling, and human diseases 总被引:9,自引:0,他引:9
Delmas P Padilla F Osorio N Coste B Raoux M Crest M 《Biochemical and biophysical research communications》2004,322(4):1374-1383
Autosomal dominant polycystic kidney disease (ADPKD) is a major, inherited nephropathy affecting over 1:1000 of the worldwide population. It is a systemic condition with frequent hepatic and cardiovascular manifestations in addition to the progressive development of fluid-filled cysts from the tubules and collecting ducts of affected kidneys. The pathogenesis of cyst formation is currently thought to involve increased proliferation of epithelial cells, mild dedifferentiation, and fluid accumulation. In the past decade, study of ADPKD led to the discovery of a unique family of highly complex proteins, the polycystins. Loss-of-function mutations in either of two polycystin proteins, polycystin-1 or polycystin-2, give rise to ADPKD. These proteins are thought to function together as part of a multiprotein complex that may initiate Ca2+ signals, directing attention to the regulation of intracellular Ca2+ as a possible misstep that participates in cyst formation. Here we review what is known about the Ca2+ signaling functions of polycystin proteins and focus on findings that have significantly advanced our physiological insight. Special attention is paid to the recently discovered role of these proteins in the mechanotransduction of the renal primary cilium and the model it suggests. 相似文献
18.
Iain A. Drummond 《生物化学与生物物理学报:疾病的分子基础》2011,1812(10):1322-1326
Polycystic kidney disease is the most common heritable disease in humans. In addition to epithelial cysts in the kidney, liver and pancreas, patients with autosomal dominant polycystic kidney disease (ADPKD) also suffer from abdominal hernia, intracranial aneurysm, gastrointestinal cysts, and cardiac valvular defects, conditions often associated with altered extracellular matrix production or integrity. Despite more than a decade of work on the principal ADPKD genes, PKD1 and PKD2, questions remain about the basis of cystic disease and the role of extracellular matrix in ADPKD pathology. This review explores the links between polycystins, focal adhesions, and extracellular matrix gene expression. These relationships suggest roles for polycystins in cell-matrix mechanosensory signaling that control matrix production and morphogenesis. This article is part of a Special Issue entitled: Polycystic Kidney Disease. 相似文献
19.
P J Foxall R G Price J K Jones G H Neild F D Thompson J K Nicholson 《Biochimica et biophysica acta》1992,1138(4):305-314
High field 1H-NMR spectra of fluid collected from the cysts of six renal transplant recipients with autosomal dominant polycystic kidney disease (ADPKD) have been measured and the major metabolite signals assigned. Quantitative NMR measurements have revealed a combination of unusual biochemical features of the cystic fluids that shows them to be distinct from both blood plasma and urine. Isoleucine, lysine, threonine and valine were present at mM concentrations, in cyst fluid and in some cases levels up to 2 orders of magnitude higher than normal plasma or urine were recorded. Mean glucose concentrations in the cyst fluids ranged from 3.4-9.6 mM and a number of organic acids and bases, including acetate, lactate, succinate, creatinine and dimethylamine were also present at high concentration and in different ratios to those found in either plasma or urine. The majority of cyst fluids examined also contained significant quantities of glycoproteins with characteristic 1H-NMR signals from N-acetyl groups of amino-sugar and sialic acid side chains which had a high degree of molecular mobility (as indicated by their relatively long T2 relaxation times, greater than 120 ms). High levels of ethanol (0.5-12.6 mM/l) were found in all fluid samples from the six transplanted patients (confirmed by conventional analysis). In general there was little variation in the 1H-NMR spectral patterns of either the intra- or interpatient cyst fluids, although the contribution of the protein macromolecules to individual spectra was lower in a few cysts. This constancy of biochemical composition probably reflects the chronic nature of the accumulation of cyst fluid and a long turnover of the cystic fluid components which has the effect of averaging composition. These findings suggest that the dynamic composition of cyst fluid from ADPKD patients is unique among the other body fluids and that the unusual composition may be related to epithelial polarity reversal of the cystic epithelium which could also contribute to the growth of the cysts. 相似文献
20.
The exocyst localizes to the primary cilium in MDCK cells 总被引:4,自引:0,他引:4
Rogers KK Wilson PD Snyder RW Zhang X Guo W Burrow CR Lipschutz JH 《Biochemical and biophysical research communications》2004,319(1):138-143
Primary cilia play a role in the maintenance of tubular epithelial differentiation and ciliary dysfunction can result in abnormal cyst formation, such as occurs in autosomal dominant polycystic kidney disease (ADPKD). We previously showed that the exocyst, an eight-protein complex involved in the biogenesis of polarity from yeast to mammals, is centrally involved in cyst formation [Mol. Biol. Cell. 11 (2000) 4259]. Here we show that the exocyst complex localizes to the primary cilium in Madin-Darby canine kidney (MDCK) tubular epithelial cells. We further show that the exocyst is overexpressed in both cell lines and primary cell cultures of ADPKD origin, suggesting that the exocyst may be involved in the pathogenesis of ADPKD. 相似文献