2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

This Article Full Text Full Text (PDF) All Versions of this Article: ASN.2007121292v1 19/6/1071    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Winn, M. P. Search for Related Content PubMed PubMed Citation Articles by Winn, M. P.

2007 Young Investigator Award: TRP'ing into a New Era for Glomerular Disease

Department of Medicine and Center for Human Genetics, Duke University Medical Center, Durham, North Carolina

Correspondence: Dr. Michelle P. Winn, Duke University Medical Center, Duke Box 2903, Durham, NC 27705. Phone: 919-660-2183; Fax: 919-684-0920; E-mail: michelle.winn{at}duke.edu

FSGS is a pathologic lesion that frequently causes the nephrotic syndrome and ensuing renal failure. The cause remains unknown in the majority of individuals; however, in the past two decades, rare familial forms have been identified. It has been suggested that known genetic causes of the hereditary form of this disease account for upwards of 18% of cases. Mutations in five genes have been found to cause inherited nephrotic syndromes and FSGS. In this article, I discuss the phenotypic characteristics of hereditary FSGS and the transient receptor potential cation channel 6 (TRPC6) protein, which is the genetic impetus for an autosomal dominant form of FSGS. The TRP channels have been implicated in varied biologic functions such as mechanosensation, ion homeostasis, cell growth, and phospholipase C–dependent calcium entry into cells. The mutated ion channel causes an increase in calcium transients. Current evidence also suggests that blocking TRPC6 channels may be of therapeutic benefit in idiopathic FSGS, a disease with a generally poor prognosis. Preliminary experiments reveal that the commonly used immunosuppressive agent FK-506 can inhibit TRPC6 activity in vivo. This creates the intriguing possibility that blocking TRPC6 channels within the podocyte may translate into long-lasting clinical benefits in patients with FSGS.

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673