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.2006091010v1 18/1/29    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 HighWire Citing Articles via Google Scholar Google Scholar Articles by Möller, C. C. Articles by Reiser, J. Search for Related Content PubMed PubMed Citation Articles by Möller, C. C. Articles by Reiser, J.

Induction of TRPC6 Channel in Acquired Forms of Proteinuric Kidney Disease

Clemens C. Möller^*, Changli Wei^*, Mehmet M. Altintas^*, Jing Li^*, Anna Greka^*, Takamoto Ohse, Jeffrey W. Pippin, Maria P. Rastaldi, Stefan Wawersik, Susan Schiavi, Anna Henger^||, Matthias Kretzler^||, Stuart J. Shankland and Jochen Reiser^*

^* Department of Medicine, Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts; Division of Nephrology, University of Washington, Seattle, Washington; Renal Immunopathology Laboratory, Associazione Nuova Nefrologia and Fondazione D’Amico per la Ricerca sulle Malattie Renali, c/o San Carlo Borromeo Hospital, Milan, Italy; Endocrine and Renal Sciences, Genzyme Corporation, Framingham, Massachusetts; and ^|| Nephrologisches Zentrum, Medizinische Poliklinik, Ludwig-Maximilians-Universität München, Munich, Germany

Address correspondence to: Dr. Jochen Reiser, Department of Medicine, Nephrology Division, Massachusetts General Hospital and Harvard Medical School, MGH-East, 149 13th Street, Boston, MA 02129. Phone: 617-726-9363; Fax: 617-726-5669; E-mail: jreiser{at}partners.org

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.

This article has been cited by other articles:

				B. Hartleben, H. Schweizer, P. Lubben, M. P. Bartram, C. C. Moller, R. Herr, C. Wei, E. Neumann-Haefelin, B. Schermer, H. Zentgraf, et al. Neph-Nephrin Proteins Bind the Par3-Par6-Atypical Protein Kinase C (aPKC) Complex to Regulate Podocyte Cell Polarity J. Biol. Chem., August 22, 2008; 283(34): 23033 - 23038. [Abstract] [Full Text] [PDF]

				E. Y. Kim, K.-J. Choi, and S. E. Dryer Nephrin binds to the COOH terminus of a large-conductance Ca2+-activated K+ channel isoform and regulates its expression on the cell surface Am J Physiol Renal Physiol, July 1, 2008; 295(1): F235 - F246. [Abstract] [Full Text] [PDF]

				S. Graham, M. Ding, S. Sours-Brothers, T. Yorio, J.-X. Ma, and R. Ma Downregulation of TRPC6 protein expression by high glucose, a possible mechanism for the impaired Ca2+ signaling in glomerular mesangial cells in diabetes Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1381 - F1390. [Abstract] [Full Text] [PDF]

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