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2017 ; 7
(1
): 4145
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Increased glomerular filtration rate and impaired contractile function of
mesangial cells in TRPC6 knockout mice
#MMPMID28646178
Li W
; Ding Y
; Smedley C
; Wang Y
; Chaudhari S
; Birnbaumer L
; Ma R
Sci Rep
2017[Jun]; 7
(1
): 4145
PMID28646178
show ga
The present study was conducted to determine if TRPC6 regulates glomerular
filtration rate (GFR) and the contractile function of glomerular mesangial cells
(MCs). GFR was assessed in conscious TRPC6 wild type and knockout mice, and in
anesthetized rats with and without in vivo knockdown of TRPC6 in kidneys. We
found that GFR was significantly greater, and serum creatinine level was
significantly lower in TRPC6 deficient mice. Consistently, local knockdown of
TRPC6 in kidney using TRPC6 specific shRNA construct significantly attenuated Ang
II-induced GFR decline in rats. Furthermore, Ang II-stimulated contraction and
Ca(2+) entry were significantly suppressed in primary MCs isolated from TRPC6
deficient mice, and the Ca(2+) response could be rescued by re-introducing TRPC6.
Moreover, inhibition of reverse mode of Na(+)-Ca(2+) exchange by KB-R7943
significantly reduced Ca(2+) entry response in TRPC6-expressing, but not in
TRPC6-knocked down MCs. Ca(2+) entry response was also significantly attenuated
in Na(+) free solution. Single knockdown of TRPC6 and TRPC1 resulted in a
comparable suppression on Ca(2+) entry with double knockdown of both. These
results suggest that TRPC6 may regulate GFR by modulating MC contractile function
through multiple Ca(2+) signaling pathways.
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