瞬时受体电位阳离子通道蛋白6在肾脏疾病中的研究进展

瞬时受体电位阳离子通道蛋白6(TRPC6)在细胞钙信号通路传导中发挥了非常重要的作用.TRPC6为重要的足细胞膜蛋白并在维系足细胞正常生物学功能中起到重要作用,TRPC6基因突变在临床上能引起蛋白尿的发生,使肾小球硬化.本文就TRPC6的结构和功能以及与肾脏相关疾病的关系的研究进展作一综述.     

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。     

Notch信号与肾脏疾病

Notch信号通路是一个在无脊椎动物和脊椎动物中广泛存在的信号通路,参与了细胞增殖、迁移、分化、血管生成等多种重要功能,与肾脏多种疾病如糖尿病肾病、肾脏肿瘤、肾功能衰竭的发生发展密切相关,了解Notch在这些疾病中的发病机制,有助于寻求新的治疗方法.     

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。     

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。     

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.     

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。     

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。     

Chloride channel mutations in hypercalciuric kidney stone disease

Recent advances in molecular biology have characterized a new class of chloride channels that are referred to as voltage-gated chloride channels. To date, 9 such voltage-gated chloride channels have been identified in mammals. These are CLC-1 to CLC-7, CLC-Ka, and CLC-Kb, which are encoded by the genesCLCN1 toCLCN7, CLCNKA, andCLCNKB, respectively. Mutations in 2 of these genes, referred to asCLCN5 andCLCNKB, have been defined in the hypercalciuric nephrolithiasis disorders of Dent's disease and a form of Bartter's syndrome, respectively. In addition, other forms of Bartter's syndrome have been defined, with mutations involving the bumetanide-sensitive sodium-potassium-chloride cotransporter (NKCC2) and the potassium channel, ROMK. Finally, mutations of the thiazide-sensitive sodium chloride cotransporter (NCCT) are associated with Gitelman's syndrome, in which hypocalciuria and hypomagnesemia are notable features. These molecular genetic studies have increased our understanding of the renal tubular mechanisms that regulate mineral homeostasis. This paper was presented at the 2nd International Forum “The Frontiers of Nephrology,” Tokyo, May 10, 1998.     

Induction of TRPC6 channel in acquired forms of proteinuric kidney disease

Injury to podocytes and their slit diaphragms typically leads to marked proteinuria. Mutations in the TRPC6 gene that codes for a slit diaphragm-associated, cation-permeable ion channel have been shown recently to co-segregate with hereditary forms of progressive kidney failure. Herein is shown that induced expression of wild-type TRPC6 is a common feature of human proteinuric kidney diseases, with highest induction observed in membranous nephropathy. Cultured podocytes that are exposed to complement upregulate TRPC6 protein. Stimulation of receptor-operated channels in puromycin aminonucleoside-treated podocytes leads to increased calcium influx in a time- and dosage-dependent manner. Mechanistically, it is shown that TRPC6 is functionally connected to the podocyte actin cytoskeleton, which is rearranged upon overexpression of TRPC6. Transient in vivo gene delivery of TRPC6 into mice leads to expression of TRPC6 protein at the slit diaphragm and causes proteinuria. These studies suggest the involvement of TRPC6 in the pathology of nongenetic forms of proteinuric disease.     

Calcium channel inhibition accelerates polycystic kidney disease progression in the Cy/+ rat

In polycystic kidney disease, abnormal epithelial cell proliferation is the main factor leading to cyst formation and kidney enlargement. Cyclic AMP (cAMP) is mitogenic in cystic but antimitogenic in normal human kidney cells, which is due to reduced steady-state intracellular calcium levels in cystic compared to the normal cells. Inhibition of intracellular calcium entry with channel blockers, such as verapamil, induced cAMP-dependent cell proliferation in normal renal cells. To determine if calcium channel blockers have a similar effect on cell proliferation in vivo, Cy/+ rats, a model of dominant polycystic kidney disease, were treated with verapamil. Kidney weight and cyst index were elevated in verapamil-treated Cy/+ rats. This was associated with increased cell proliferation and apoptosis, elevated expression, and phosphorylation of B-Raf with stimulation of the mitogen-activated protein kinase MEK/ERK (mitogen-activated protein kinase kinase/extracellular-regulated kinase) pathway. Verapamil had no effect on kidney morphology or B-Raf stimulation in wild-type rats. We conclude that treatment of Cy/+ rats with calcium channel blockers increases activity of the B-Raf/MEK/ERK pathway accelerating cyst growth in the presence of endogenous cAMP, thus exacerbating renal cystic disease.     

Subclinical celiac disease and crystal-induced kidney disease following kidney transplant

Decreased kidney function from kidney deposition of calcium oxalate has been described previously in inflammatory bowel disease and after jejuno-ileal and Roux-en-Y gastric bypass surgeries. Although celiac disease is the most prevalent bowel abnormality associated with intestinal malabsorption, its relationship to high kidney oxalate burden and decreased kidney function has not been established. We report a case of subclinical celiac disease and hyperoxaluria that presented with loss of kidney function as a result of high oxalate load in the absence of overt diarrhea, documented intestinal fat malabsorption, and nephrolithiasis. Subclinical celiac disease is commonly overlooked and hyperoxaluria is not usually investigated in kidney patients. We propose that this entity should be suspected in patients with chronic kidney disease in which the cause of kidney damage has not been clearly established.     

埃兹蛋白与肾脏病

埃兹蛋白(Ezrin)是肾脏足细胞活化和损伤的标志性蛋白,近期研究表明ezrin表达异常可导致足细胞脱落,并与肾小球疾病的预后有关,而ezrin磷酸化异常又与狼疮性肾炎时T细胞归巢异常有关.本文对近年ezrin在肾病的研究做一综述.     

Acupuncture and kidney disease

Acupuncture as a complex therapeutic system has been used to treat a variety of diseases and pathological conditions. Although the exact mechanism(s) of acupuncture remains unknown, some evidence suggests a mechanism initially involving signal transduction through connective tissue, with secondary involvement of other systems including the nervous system. Acupuncture has become increasingly popular in the Western countries as a therapy for pain and several chronic disorders difficult to manage with conventional treatments. Acupuncture and acupuncture-like somatic nerve stimulation have been used in different kidney diseases and several complications related to them. The effect of acupuncture techniques in some kidney diseases is reviewed on the basis of clinical reports as well as mechanisms that may possibly explain the beneficial effects mediated by acupressure/acupuncture. The potential effect of acupressure techniques in renal inflammation and whether these effects could be mediated through the newly identified cholinergic anti-inflammatory pathway are discussed.     

埃兹蛋白与肾脏病

埃兹蛋白(Ezrin)是肾脏足细胞活化和损伤的标志性蛋白,近期研究表明ezrin表达异常可导致足细胞脱落,并与肾小球疾病的预后有关,而ezrin磷酸化异常又与狼疮性肾炎时T细胞归巢异常有关.本文对近年ezrin在肾病的研究做一综述.     

Hypertension and kidney disease

The relationship between chronic kidney disease and hypertension remains enigmatic and a matter of considerable clinical and academic interest, with evidence suggesting that hypertension is both a cause and a consequence of kidney disease. The kidney has a pivotal role in setting the blood pressure in any individual, and this is likely to be related to that individual's sensitivity to salt. The relationship between low birth weight and subsequent hypertension and kidney disease may be predicated on changes in post glomerular phenomena, including sodium transport, although there are differences observed between white and black populations, there being no such clear relationship demonstrable in the latter. Differences in vascular structure may account for some of this variation. There is , by way of example a considerable difference in the risk of death from cardiovascular disease between blacks and Caucasoid populations with renal disease, the former being at greater risk. International moves are now afoot to reduce dietary salt intake. Successful efforts to reduce blood pressure by these or by pharmacological means are likely to reduce death rates, although precise blood pressure targets remain an elusive concept. The possible role of non muscular heavy chain type II isoform A protein which is associated with non diabetic chronic kidney disease in subjects of African ancestry remains to be determined.