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 language | English |
|---|---|
| Pages (from-to) | 29-36 |
| Number of pages | 8 |
| Journal | Journal of the American Society of Nephrology |
| Volume | 18 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jan 2007 |
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ASJC Scopus subject areas
- Nephrology
Cite this
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 journal › Article
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TY - JOUR
T1 - Induction of TRPC6 channel in acquired forms of proteinuric kidney disease
AU - Möller, Clemens C.
AU - Wei, Changli
AU - Altintas, Mehmet M.
AU - Li, Jing
AU - Greka, Anna
AU - Ohse, Takamoto
AU - Pippin, Jeffrey W.
AU - Rastaldi, Maria P.
AU - Wawersik, Stefan
AU - Schiavi, Susan
AU - Henger, Anna
AU - Kretzler, Matthias
AU - Shankland, Stuart J.
AU - Reiser, Jochen
PY - 2007/1
Y1 - 2007/1
N2 - 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.
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.
UR - http://www.scopus.com/inward/record.url?scp=33846028228&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846028228&partnerID=8YFLogxK
U2 - 10.1681/ASN.2006091010
DO - 10.1681/ASN.2006091010
M3 - Article
C2 - 17167110
AN - SCOPUS:33846028228
VL - 18
SP - 29
EP - 36
JO - Journal of the American Society of Nephrology : JASN
JF - Journal of the American Society of Nephrology : JASN
SN - 1046-6673
IS - 1
ER -