RT Journal Article
SR Electronic
T1 Induction of TRPC6 Channel in Acquired Forms of Proteinuric Kidney Disease
JF Journal of the American Society of Nephrology
JO J. Am. Soc. Nephrol.
FD American Society of Nephrology
SP 29
OP 36
DO 10.1681/ASN.2006091010
VO 18
IS 1
A1 Möller, Clemens C.
A1 Wei, Changli
A1 Altintas, Mehmet M.
A1 Li, Jing
A1 Greka, Anna
A1 Ohse, Takamoto
A1 Pippin, Jeffrey W.
A1 Rastaldi, Maria P.
A1 Wawersik, Stefan
A1 Schiavi, Susan
A1 Henger, Anna
A1 Kretzler, Matthias
A1 Shankland, Stuart J.
A1 Reiser, Jochen
YR 2007
UL http://jasn.asnjournals.org/content/18/1/29.abstract
AB 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.