Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice

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dc.creatorLi, Weizu
dc.creatorDing, Yanfeng
dc.creatorSmedley, Crystal
dc.creatorWang, Yanxia
dc.creatorChaudhari, Sarika
dc.creatorBirnbaumer, Lutz
dc.creatorMa, Rong
dc.date.accessioned2022-09-30T17:34:19Z
dc.date.available2022-09-30T17:34:19Z
dc.date.issued2017-06-23
dc.description.abstractThe 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.
dc.description.sponsorshipThe work was supported by National Institutes of Health (NIH/NIDDK) Grant RO1 (5RO1DK079968, to R. Ma), by Grant-in-Aid from American Heart Association Southwestern Affiliate (16GRNT27780043, to R. Ma) and by the Intramural Research Program of the NIH (Project Z01-ES101684 to L. Birnbaumer).
dc.identifier.citationLi, W., Ding, Y., Smedley, C., Wang, Y., Chaudhari, S., Birnbaumer, L., & Ma, R. (2017). Increased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice. Scientific reports, 7(1), 4145. https://doi.org/10.1038/s41598-017-04067-z
dc.identifier.issn2045-2322
dc.identifier.issue1
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31826
dc.identifier.volume7
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/s41598-017-04067-z
dc.rights.holder© The Author(s) 2017
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.subject.meshAlbuminuria / genetics
dc.subject.meshAlbuminuria / urine
dc.subject.meshAngiotensin II / metabolism
dc.subject.meshAngiotensin II / pharmacology
dc.subject.meshAnimals
dc.subject.meshArterial Pressure
dc.subject.meshCalcium / metabolism
dc.subject.meshCalcium Signaling
dc.subject.meshGlomerular Filtration Rate / drug effects
dc.subject.meshGlomerular Filtration Rate / genetics
dc.subject.meshMale
dc.subject.meshMesangial Cells / metabolism
dc.subject.meshMice
dc.subject.meshMice, Knockout
dc.subject.meshRats
dc.subject.meshSodium-Calcium Exchanger / genetics
dc.subject.meshSodium-Calcium Exchanger / metabolism
dc.subject.meshTRPC6 Cation Channel / genetics
dc.subject.meshVasoconstriction / genetics
dc.titleIncreased glomerular filtration rate and impaired contractile function of mesangial cells in TRPC6 knockout mice
dc.typeArticle
dc.type.materialtext

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