TRPC6 and kidney

编码瞬时受体潜势阳离子通道TRPC6的显性突变已在22个家系中被鉴定，导致遗传性局灶性节段性肾小球硬化(FSGS)。最初的功能分析导致了这样的概念，即TRPC6的功能获得突变是导致FSGS发生的原因。这项研究项目涉及分析TRPC6的新突变，这种突变分离于患有FSGS的人类。应该澄清的是，TRPC6功能缺失突变是否可能导致人类FSGS，并可能与儿童早期FSGS有关。这些研究有助于更好地了解TRPC6在人类蛋白尿综合征发展中的作用。建议的研究表明，TRPC6在人类FSGS中的作用发生了范式转变。TRPC6的药理靶向可能是治疗肾小球裂隙膜功能障碍和蛋白尿的一种新方法。

Dominant mutations in TRPC6 encoding the transient receptor potential cation channel TRPC6 have been identified in 22 families to cause hereditary focal segmental glomerulosclerosis (FSGS). Initial functional analyzes have led to the concept that gain-of-function mutations in TRPC6 are responsible for the development of FSGS. This research project deals with the analysis of novel mutations in TRPC6, which segregate in humans with FSGS. It should be clarified whether loss-of-function mutations in TRPC6 may lead to FSGS in humans and may be associated with early FSGS in childhood. The investigations serve to better understand the role of TRPC6 in the development of proteinuric syndromes in humans. The suggested studies suggest a paradigm shift on the role of TRPC6 in FSGS in man. Pharmacological targeting of TRPC6 may represent a novel approach to treat dysfunction of the glomerular slit membrane and proteinuria.