Deciphering the SUMO code in the kidney

SUMOylation of proteins is an important regulatory element in modulating protein function and has been implicated in the pathogenesis of numerous human diseases such as cancers, neurodegenerative diseases, brain injuries, diabetes, and familial dilated cardiomyopathy. Growing evidence has pointed to a significant role of SUMO in kidney diseases such as DN, RCC, nephritis, AKI, hypertonic stress and nephrolithiasis. Recently, emerging studies in podocytes demonstrated that SUMO might have a protective role against podocyte apoptosis. However, the SUMO code responsible for beneficial outcome in the kidney remains to be decrypted. Our recent experiments have revealed that the expression of both SUMO and SUMOylated proteins is appreciably elevated in hypoxia‐induced tubular epithelial cells (TECs) as well as in the unilateral ureteric obstruction (UUO) mouse model, suggesting a role of SUMO in TECs injury and renal fibrosis. In this review, we attempt to decipher the SUMO code in the development of kidney diseases by summarizing the defined function of SUMO and looking forward to the potential role of SUMO in kidney diseases, especially in the pathology of renal fibrosis and CKD, with the goal of developing strategies that maximize correct interpretation in clinical therapy and prognosis.     

Tissue engineering of a bioartificial kidney

Tissue engineering is a rapidly growing field in biotechnology. The use and packaging of synthetic materials, biologic compounds, and cellular components of specific tissues can be envisioned to replace physiologic function of diseased organs. Long-term ex vivo therapy for kidney failure has been achieved, so that the kidney may be the first solid organ in which tissue engineering concepts can produce an implantable device for long-term in vivo replacement therapy. To replace the kidney's excretory function, an implantable bioartificial kidney requires both a device to replace blood ultrafiltration performed by renal glomeruli and a device to replace transport regulatory function of the renal tubule. The initial concepts for these devices are just beginning to be considered and developed. (c) 1994 John Wiley & Sons, Inc.     

Emerging role of autophagy in kidney function,diseases and aging

Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy.     

Emerging role of autophagy in kidney function,diseases and aging

Autophagy is a highly conserved process that degrades cellular long-lived proteins and organelles. Accumulating evidence indicates that autophagy plays a critical role in kidney maintenance, diseases and aging. Ischemic, toxic, immunological, and oxidative insults can cause an induction of autophagy in renal epithelial cells modifying the course of various kidney diseases. This review summarizes recent insights on the role of autophagy in kidney physiology and diseases alluding to possible novel intervention strategies for treating specific kidney disorders by modifying autophagy.     

Are Bans on Kidney Sales Unjustifiably Paternalistic?

This paper challenges the view that bans on kidney sales are unjustifiably paternalistic, that is, that they unduly deny people the freedom to make decisions about their own bodies in order to protect them from harm. I argue that not even principled anti‐paternalists need to reject such bans. This is because their rationale is not hard paternalism, which anti‐paternalists repudiate, but soft paternalism, which they in principle accept. More precisely, I suggest that their rationale is what Franklin Miller and Alan Wertheimer call ‘group soft paternalism’. Group soft paternalistic policies restrict the freedom of autonomous individuals, not for their own good (hard paternalism), but as an unavoidable consequence of seeking to protect other, non‐autonomous individuals from harms that they have not voluntarily chosen (soft paternalism). Group soft paternalism supports prohibiting kidney sales on three conditions: (1) that such sales are potentially harmful to vendors, (2) that many vendors would suffer impaired autonomy, and (3) that distinguishing between autonomous and non‐autonomous vendors and interfering only with the latter is unfeasible. I provide reasons for thinking that these conditions will often hold.     

Zebrafish kidney development: basic science to translational research

The zebrafish has become a significant model system for studying renal organogenesis and disease, as well as for the quest for new therapeutics, because of the structural and functional simplicity of the embryonic kidney. Inroads to the nature and disease states of kidney-related ciliopathies and acute kidney injury (AKI) have been advanced by zebrafish studies. This model organism has been instrumental in the analysis of mutant gene function for human disease with respect to ciliopathies. Additionally, in the AKI field, recent work in the zebrafish has identified a bona fide adult zebrafish renal progenitor (stem) cell that is required for neo-nephrogenesis, both during the normal lifespan and in response to renal injury. Taken together, these studies solidify the zebrafish as a successful model system for studying the broad spectrum of ciliopathies and AKI that affect millions of humans worldwide, and point to a very promising future of zebrafish drug discovery. The emphasis of this review will be on the role of the zebrafish as a model for human kidney-related ciliopathies and AKI, and how our understanding of these complex pathologies is being furthered by this tiny teleost.     

MXRA5 is a TGF‐β1‐regulated human protein with anti‐inflammatory and anti‐fibrotic properties

Current therapy for chronic kidney disease (CKD) is unsatisfactory because of an insufficient understanding of its pathogenesis. Matrix remodelling‐associated protein 5 (MXRA5, adlican) is a human protein of unknown function with high kidney tissue expression, not present in rodents. Given the increased expression of MXRA5 in injured tissues, including the kidneys, we have suggested that MXRA5 may modulate kidney injury. MXRA5 immunoreactivity was observed in tubular cells in human renal biopsies and in urine from CKD patients. We then explored factors regulating MXRA5 expression and MXRA5 function in cultured human proximal tubular epithelial cells and explored MXRA5 expression in kidney cancer cells and kidney tissue. The fibrogenic cytokine transforming growth factor‐β1 (TGFβ1) up‐regulated MXRA5 mRNA and protein expression. TGFβ1‐induced MXRA5 up‐regulation was prevented by either interference with TGFβ1 activation of the TGFβ receptor 1 (TGFBR1, ALK5) or by the vitamin D receptor agonist paricalcitol. By contrast, the pro‐inflammatory cytokine TWEAK did not modulate MXRA5 expression. MXRA5 siRNA‐induced down‐regulation of constitutive MXRA5 expression resulted in higher TWEAK‐induced expression of chemokines. In addition, MXRA5 down‐regulation resulted in a magnified expression of genes encoding extracellular matrix proteins in response to TGFβ1. Furthermore, in clear cell renal cancer, von Hippel–Lindau (VHL) regulated MXRA5 expression. In conclusion, MXRA5 is a TGFβ1‐ and VHL‐regulated protein and, for the first time, we identify MXRA5 functions as an anti‐inflammatory and anti‐fibrotic molecule. This information may yield clues to design novel therapeutic strategies in diseases characterized by inflammation and fibrosis.     

Structure Organization of Urinary System in the Yellow Spotted Mountain Newts （Salamandridae： Neurergus microspilotus）

This study deals with the histomorphology of the mesonephros in male and female Neurergus microspilotus. The slender and narrow kidneys are positioned in the retro peritoneal position up against the ventral aspect of vertebral column and may extend the length from the esophagus-stomach junction to cloaca. The kidney in both sexes is composed of sexual（anterior） and pelvic（posterior） parts. The duct of sexual kidney is a narrow duct which is lying alongside its lateral edge. In the female, it is connected to the ureters and then the duct of defi nitive kidney. Before entering the cloaca, two ureters are joined together and open to the apex of the cloaca. In the male, after entering the sexual kidney, the sperm leave the testis through efferent ducts, then these ducts join together and eventually form Bidder＇s duct. The Bidder＇s duct joins the Bowman＇s capsule of the nephrons in the sexual kidney and the nephrons make collecting ducts which are fi lled with both sperm and urine. After leaving the kidney, all the collecting ducts are connected to the Wolffi an duct. Wolffi an duct joins the ureters（merge from defi nitive kidney） just before entering the cloaca. Based on serial paraffi n sections, nephrons consist of a fi ltration unit, the Malpighian corpuscle, and a renal tubule, which can be divided into 4 morphologically distinct segments： proximal tubule（first and second segment）, distal tubule, and collecting tubule. Collecting tubules merge and form a branch system that opens into collecting ducts.     

Antithrombin III prevents progression of chronic kidney disease following experimental ischaemic‐reperfusion injury

Acute kidney disease (AKI) leads to increased risk of progression to chronic kidney disease (CKD). Antithrombin III (ATIII) is a potent anticoagulant with anti‐inflammatory properties, and we previously reported that insufficiencies of ATIII exacerbated renal ischaemia‐reperfusion injury (IRI) in rats. In this study, we examined the characteristic of AKI‐CKD transition in rats with two distinct AKI models. Based on our observation, left IRI plus right nephrectomy (NX‐IRI) was used to determine whether ATIII had therapeutic effects in preventing CKD progression after AKI. It was observed that NX‐IRI resulted in significant functional and histological damage at 5 weeks after NX‐IRI compared with sham rats, which was mitigated by ATIII administration. Besides, we noticed that ATIII administration significantly reduced NX‐IRI‐induced interstitial fibrosis. Consistently, renal expression of collagen‐1, α‐smooth muscle actin and fibronectin were substantial diminished in ATIII‐administered rats compared with un‐treated NX‐IRI rats. Furthermore, the beneficial effects of ATIII were accompanied with decreased M1‐like macrophage recruitment and down‐regulation of M1‐like macrophage‐dependent pro‐inflammatory cytokines such as tumour necrosis factor α, inducible nitric oxide synthase and interleukin‐1β, indicating that ATIII prevented AKI‐CKD transition via inhibiting inflammation. Overall, ATIII shows potential as a therapeutic strategy for the prevention of CKD progression after AKI.     

中国内江猪肾脏的解剖学研究

根据医学异种移植研究的需要, 选取５ —６ 月龄中国内江猪１９ 头, 处死后甲醛固定肾脏标本, 进行测量并与国人肾脏解剖学资料对比, 以了解中国内江猪肾脏解剖学特点及与国人肾脏的差别。结果表明内江猪肾脏与国人肾脏无大的解剖学差异, 并具有分支型、迷走型肾动脉出现率低的优点。认为从解剖学角度看, 中国内江猪肾脏完全符合异种移植的要求。     

根据“肠-肾轴”理论治疗慢性肾脏病的研究进展

有研究报道在慢性肾脏病的发生发展过程中可发现一系列肠道变化,并有学者用"肠-肾轴"理论阐述肾脏病中肠道的变化以及疾病过程中肾脏与肠道之间的联系,提示调节肠道菌群或可成为治疗慢性肾脏病的新方法。本文根据"肠-肾轴"理论,综述了在慢性肾脏病发展过程中肠道出现的变化,如肠内代谢物异常、肠道损伤以及肠道菌群失调等。以慢性肾脏病发生发展过程中肠道的异常变化为治疗切入点,总结了以大黄为主的中药在调节肠道功能、修复肠道屏障、纠正肠道代谢物异常等方面具有的显著疗效,为治疗慢性肾脏病及减少并发症等提供新的治疗思路和新方法。     

Mild ischemic Injury Leads to Long-Term Alterations in the Kidney: Amelioration by Spironolactone Administration

Administration of the mineralocorticoid receptor antagonist spironolactone prevents the development of chronic kidney disease (CKD) after a severe ischemic injury. However, whether brief periods of ischemia lead to CKD and whether spironolactone administration after ischemia may be a useful therapeutic strategy to prevent the gradual deterioration of structure and function remains unexplored.Nineteen male Wistar rats were divided into four groups: rats that underwent renal bilateral ischemia for 10, 20, or 45 min were compared with sham operated rats. Additionally, thirteen male Wistar rats that underwent renal bilateral ischemia for 20 min were divided into an untreated ischemic group (I) and two groups receiving spironolactone, 20 mg/kg by gavage, at either 0 (Sp0) or 1.5-h after ischemia (Sp1.5). The rats were followed up and studied after 9 months.Mild (20 min) and severe (45 min) ischemia induced a progressive increase in proteinuria at varying magnitudes, whereas minor ischemia (10 min) did not modify proteinuria. CKD induced by moderate ischemia was characterized by renal hypertrophy and tubulointerstitial fibrosis. These effects were associated with activation of the transforming growth factor β (TGFβ) signaling pathway and up-regulation of endothelin receptor A (ETA) and alpha smooth muscle actin (αSMA). Spironolactone treatment immediately or 1.5-h after the ischemic insult prevented the onset of these disorders.Our results show that moderate ischemic insult leads to long-term structural and molecular changes that may compromise renal function in later stages. Additionally, we demonstrate that spironolactone administration after mild ischemia prevents this detrimental effect.     

Pax2在肾脏发育和肾疾病中的调控作用

配对盒基因2(Paired box2,Pax2)是肾脏发育中重要的转录因子,在前、中、后肾发育的全过程表达,集中分布在发育的各级小管和间充质成分,具有特定的时空特性。研究表明Pax2与多种调节肾脏发育的因子Gdnf、Ret、SHH、Wnt4及Fgf等相互作用,共同精准诱导生肾索形成,前/中肾管的形成及分化,输尿管芽的发生及分支,肾单位的诱导分化。Pax2的变异导致多种先天性肾脏及输尿管发育畸形,最易发生在肾-视神经盘缺损综合征。在肾细胞癌、Wilms瘤和多种肾小球及肾小管获得性疾病中存在Pax2的异常表达,其诊断和治疗价值将是今后研究的重点。文章主要对Pax2的分子结构、在肾脏发育和肾疾病的表达及调控进行了综述。     

Nephroblastomatosis and nephroblastoma in nonhuman primates

Wilms' tumors, or nephroblastomas, are renal embryonal malignancies with a high incidence in humans. Nephroblastomas are uncommon in nonhuman primates. This report describes three cases of spontaneous proliferative renal tumors in young monkeys: two cases of unilateral kidney nephroblastomas in baboons and a nephroblastomatosis in a cynomolgus macaque. Histologically, both baboon tumors were typical of Wilms' tumors found in humans, with proliferative epithelial cells forming tubules and aborted glomeruli, nephrogenic rests and proliferative fibrovascular tissue. The left kidney of the macaque was markedly enlarged and histologically similar to the baboon tumors, although normal kidney architecture was completely effaced by primitive tubules and occasional glomeruli surrounded by edematous stromal tissue. Cytogenetic analysis did not detect any macaque or baboon equivalents to human Wilms' tumor chromosomal abnormalities. By human pathology classification, the diffuse nature of the macaque tumor is more consistent with nephroblastomatosis than nephroblastoma. This differentiation is the first to be reported in a species other than human. The nephroblastomas described here are the first nephroblastomas to be reported in baboons. Our observations indicate that nonhuman primate nephroblastomatosis and nephroblastomas develop in a similar way to Wilms' tumors in humans, although no genetic marker has been associated with nephroblastomas of nonhuman primates thus far.     

Crossed renal ectopia in a squirrel monkey (Saimiri sciureus) and an owl monkey (Aotus trivirgatus)

A 5-year-old female squirrel monkey, Saimiri sciureus, died with a ceco-colonic infarct. An incidental finding was renal ectopia: The left kidney was located between the common iliac arteries posterior to the bifurcation of the aorta and to the right of the body midline. An adult owl monkey, Aotus trivirgatus, was killed in renal failure due to end-stage glomerulonephritis. Fused kidneys were located on the right side and posterior to the normal position. These are examples of crossed renal ectopia with and without fusion.     

A rapid procedure for the isolation of lysosomes from kidney cortex by Percoll density gradient centrifugation

Highly pure lysosomes were isolated from buffalo(Bubalus bubalis) kidney cortex by a procedure involving differential and isopycnic Percoll density gradient centrifugations. Arylsulphatase, N-acetyl-Β-glucosamindase and cathepsin D in the lysosomal preparation were 26–45-fold enriched over the homogenate. The purified lysosomes contained less than 0·06% of mitochondrial, microsomal and peroxisomal marker enzymes. In the electron micrographs the particles appeared as large dense granules of size 0·3-1·9 μm with no apparent structural features belonging to mitochondria or microsomes. The isolation procedure was also found to be suitable to obtain highly pure lysosome particles from renal cortex of other sources such as rat, lamb and beef. No ultracentrifugation steps were involved in the procedure