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, Jochen Reiser

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)29-36
Number of pages8
JournalJournal of the American Society of Nephrology
Volume18
Issue number1
DOIs
Publication statusPublished - Jan 2007

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Podocytes
Kidney Diseases
Diaphragm
Proteinuria
Puromycin Aminonucleoside
Membranous Glomerulonephritis
Actin Cytoskeleton
Ion Channels
Genes
Renal Insufficiency
Cations
Proteins
Up-Regulation
Pathology
Calcium
Mutation
Wounds and Injuries

ASJC Scopus subject areas

  • Nephrology

Cite this

Möller, C. C., Wei, C., Altintas, M. M., Li, J., Greka, A., Ohse, T., ... Reiser, J. (2007). Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. Journal of the American Society of Nephrology, 18(1), 29-36. https://doi.org/10.1681/ASN.2006091010

Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. / Möller, Clemens C.; Wei, Changli; Altintas, Mehmet M.; Li, Jing; Greka, Anna; Ohse, Takamoto; Pippin, Jeffrey W.; Rastaldi, Maria P.; Wawersik, Stefan; Schiavi, Susan; Henger, Anna; Kretzler, Matthias; Shankland, Stuart J.; Reiser, Jochen.

In: Journal of the American Society of Nephrology, Vol. 18, No. 1, 01.2007, p. 29-36.

Research output: Contribution to journalArticle

Möller, CC, Wei, C, Altintas, MM, Li, J, Greka, A, Ohse, T, Pippin, JW, Rastaldi, MP, Wawersik, S, Schiavi, S, Henger, A, Kretzler, M, Shankland, SJ & Reiser, J 2007, 'Induction of TRPC6 channel in acquired forms of proteinuric kidney disease', Journal of the American Society of Nephrology, vol. 18, no. 1, pp. 29-36. https://doi.org/10.1681/ASN.2006091010
Möller, Clemens C. ; Wei, Changli ; Altintas, Mehmet M. ; Li, Jing ; Greka, Anna ; Ohse, Takamoto ; Pippin, Jeffrey W. ; Rastaldi, Maria P. ; Wawersik, Stefan ; Schiavi, Susan ; Henger, Anna ; Kretzler, Matthias ; Shankland, Stuart J. ; Reiser, Jochen. / Induction of TRPC6 channel in acquired forms of proteinuric kidney disease. In: Journal of the American Society of Nephrology. 2007 ; Vol. 18, No. 1. pp. 29-36.
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