甲羟戊酸与肾脏疾病

甲羟戊酸（mevalonate，MVA）是包括胆固醇在内的一系列重要物质生物合成过程的专有前体物质，参与调节细胞增殖和胶原合成等重要的生理和病理生理过程，并与肾脏疾病的发生发展有一定的关系。     

Podocin与肾脏疾病

Podocin是一种在肾小球足细胞特异表达的跨膜蛋白，具有离子通道和信号转导功能，在足细胞形态形成和足突裂孔隔膜的结构组织与功能调节中发挥重要作用。临床遗传学研究揭示，编码podocin的基因NPHS2的突变可导致多种形式的类固醇抵抗型肾病综合征。podocin在肾小球疾病发病机制中的进一步研究，对蛋白尿相关的肾小球疾病的诊治有重要的指导意义。     

维甲酸与肾脏疾病

维甲酸是维生素A类代谢产物,有介导细胞分化、增殖、凋亡和免疫调节多种生物学活性,对多种肾脏疾病动物模型有保护作用,可能为肾脏疾病的治疗找到新的治疗方案。本文就维甲酸在肾脏疾病中的应用作一综述。     

趋化因子与肾脏疾病

综述了趋化因子的分类、趋化因子受体、信号传导途径和生物学功能，以及趋化因子与肾脏疾病的关系。     

Syndecans与肾脏疾病

Ｓｙｎｄｅｃａｎｓ是一种蛋白聚糖，可与多种多肽类生长因子结合，并参与细胞外基质及细胞与细胞之间的粘附，综述多位学者的研究证明，Ｓｙｎｄｅｃａｎｓ在肾脏疾病的发病机制中可能参与一定致病作用。     

HB-EGF与肾脏疾病

HB EGF是属于表皮生长因子家族的一种强烈的丝裂原 ,它以自分泌、旁分泌或邻分泌形式发挥其多种生物学效应。无论在体内、外实验 ,多种肾脏病变时HB EGF的产生均增加。HB EGF刺激系膜细胞、内皮细胞、肾小管细胞增殖 ,促进系膜基质合成和急性损伤小管的修复等 ,成为肾脏病变过程中的一个关键生长因子。     

他汀与肾脏疾病

他汀类药物是广泛应用于临床的经典和强效降脂药,近年的研究发现此类药物还具有不依赖于降脂作用的多方面肾脏保护作用.本文综述有关这方面的研究进展.     

Caspase与肾脏疾病

Caspase是执行细胞凋亡的主要酶类，同时它也参与了一些细胞因子的发育成熟。它通过诱导肾脏局部炎症细胞凋亡及肾脏固有细胞的凋亡和促进某些细胞因子的发育成熟对肾损伤起到了有利、有弊的双重作用。前者诱导炎症细胞凋亡，缓解症状；后两者加重炎症反应及肾损伤。本文就Caspase与肾脏疾病的关系作一综述。     

细胞粘附分子与肾脏疾病

粘附分子是介导细胞与细胞，细胞与细胞外基质粘附的一类配基或受体，细胞粘附对细胞分化组织器官的分化，免疫细胞的激活和免疫细胞间的相互作用、白细胞的再循环和迁移、以及肿瘤细胞的生长和扩散都起着重要的基本作用，在过去的十年里，粘附分子的研究进展有极其迅速，除了粘附分子的三个经典家族外，最近还报导了一类化学吸引的细胞因子，称为化学增活素，粘附分子在肾组织的表达；粘附分子在肾炎中的表达变化；抗粘附分子的单克     

The role of Notch signaling in kidney podocytes

Clinical and Experimental Nephrology - The Notch signaling pathway is a basic cell-to-cell communication mechanism. This pathway is activated by the interaction between Notch receptors and the...     

Wnt signaling in polycystic kidney disease

Wnt signaling cascades activate morphogenetic programs that range from cell migration and proliferation to cell fate determination and stem cell renewal. These pathways enable cells to translate environmental cues into the complex cellular programs that are needed to organize tissues and build organs. Wnt signaling is essential for renal development; however, the specific molecular underpinnings involved are poorly understood. Recent research has revealed an unexpected intersection between Wnt signaling and polycystic kidney disease. Some polycystic kidney disease proteins, such as Inversin and Bardet-Biedl syndrome family members, were found to use components of the Wnt signaling cascade to orient cells along a secondary polarity axis within the plane of the epithelium. These spatial cues may be needed to position nascent tubules with a defined geometry.     

The role of Notch signaling in specification of podocyte and proximal tubules within the developing mouse kidney

Notch genes encode transmembrane receptors that mediate intercellular interaction by binding to the ligands on the adjacent cells. Due to early embryonic lethality in mice deficient for some Notch pathway genes, the role of Notch signaling for kidney development has not yet been defined. Using an antibody specific to the N-terminal end of gamma-secretase-cleaved Notch 1, we found evidence for Notch 1 activation in the comma-shaped and S-shaped bodies. We therefore cultured embryonic (E) day E12.5 mouse metanephroi in the presence of a gamma-secretase inhibitor, N-S-phenyl-glycine-t-butyl ester (DAPT), to block Notch signaling. Fewer renal epithelial structures were observed, with a severe deficiency in proximal tubules and glomerular podocytes. Distal tubules were present but at a reduced number, and this was accompanied by an increase in intervening, nonepithelial cells. By culturing day E14.5 metanephroi, we observed the formation of podocyte clusters after 3 days of DAPT treatment. These observations suggest that gamma-secretase activity, probably through activation of Notch, is not essential for podocyte formation beyond the stage of S-shaped body but is required for the proximal tubule and podocyte fates when S-shaped bodies are forming.     

Wnt信号通路在肾病发病中的作用

Wnt信号通路早先发现时被认为其主要与细胞增殖旺盛的胚胎发育和肿瘤发生相关[1].目前研究发现,在肾脏发育及急性肾小管损伤中.Wnt信号通路发挥了积极的促进其发育和修复损伤的作用[2,3];但却又是多囊肾病及肾癌的关键发病机制之一[4,5].南此表明,肾脏的发育、形态以及功能的维持均有赖于Wnt信号通路正常"开启"和及时"关闭".本文就近年来Wnt信号通路在肾脏疾病发生、发展中的作用作一综述.     

Dose-dependent effects of sirolimus on mTOR signaling and polycystic kidney disease

Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal models of polycystic kidney disease (PKD); however, two clinical trials in patients with autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or progressive stages of disease. The stage of disease during treatment and the dose of mTOR inhibitors may account for these differing results. Here, we studied the effects of a conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30-60 ng/ml, respectively) on mTOR activity and renal cystic disease in two Pkd1-mutant mouse models at different stages of the disease. When initiated at early but not late stages of disease, high-dose treatment strongly reduced mTOR signaling in renal tissues, inhibited cystogenesis, accelerated cyst regression, and abrogated fibrosis and the infiltration of immune cells. In contrast, low-dose treatment did not significantly reduce renal cystic disease. Levels of p-S6Rp(Ser240/244), which marks mTOR activity, varied between kidneys; severity of the renal cystic phenotype correlated with the level of mTOR activity. Taken together, these data suggest that long-term treatment with conventional doses of sirolimus is insufficient to inhibit mTOR activity in renal cystic tissue. Mechanisms to increase bioavailability or to target mTOR inhibitors more specifically to kidneys, alone or in combination with other compounds, may improve the potential for these therapies in PKD.