TRPC6 enhances angiotensin II-induced albuminuria.

Hdl Handle:
http://hdl.handle.net/10147/237972
Title:
TRPC6 enhances angiotensin II-induced albuminuria.
Authors:
Eckel, Jason; Lavin, Peter J; Finch, Elizabeth A; Mukerji, Nirvan; Burch, Jarrett; Gbadegesin, Rasheed; Wu, Guanghong; Bowling, Brandy; Byrd, Alison; Hall, Gentzon; Sparks, Matthew; Zhang, Zhu Shan; Homstad, Alison; Barisoni, Laura; Birbaumer, Lutz; Rosenberg, Paul; Winn, Michelle P
Affiliation:
Center for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.
Citation:
TRPC6 enhances angiotensin II-induced albuminuria. 2011, 22 (3):526-35 J. Am. Soc. Nephrol.
Journal:
Journal of the American Society of Nephrology : JASN
Issue Date:
Mar-2011
URI:
http://hdl.handle.net/10147/237972
DOI:
10.1681/ASN.2010050522
PubMed ID:
21258036
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed?term=TRPC6%20enhances%20angiotensin%20II-induced%20albuminuria.%20
Abstract:
Mutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.
Item Type:
Article
Language:
en
MeSH:
Albuminuria; Angiotensin II; Animals; Calcium; Disease Models, Animal; Hypertension; Injections, Subcutaneous; Kidney; Male; Mice; Mice, Knockout; Patch-Clamp Techniques; Podocytes; TRPC Cation Channels
ISSN:
1533-3450

Full metadata record

DC FieldValue Language
dc.contributor.authorEckel, Jasonen_GB
dc.contributor.authorLavin, Peter Jen_GB
dc.contributor.authorFinch, Elizabeth Aen_GB
dc.contributor.authorMukerji, Nirvanen_GB
dc.contributor.authorBurch, Jarretten_GB
dc.contributor.authorGbadegesin, Rasheeden_GB
dc.contributor.authorWu, Guanghongen_GB
dc.contributor.authorBowling, Brandyen_GB
dc.contributor.authorByrd, Alisonen_GB
dc.contributor.authorHall, Gentzonen_GB
dc.contributor.authorSparks, Matthewen_GB
dc.contributor.authorZhang, Zhu Shanen_GB
dc.contributor.authorHomstad, Alisonen_GB
dc.contributor.authorBarisoni, Lauraen_GB
dc.contributor.authorBirbaumer, Lutzen_GB
dc.contributor.authorRosenberg, Paulen_GB
dc.contributor.authorWinn, Michelle Pen_GB
dc.date.accessioned2012-08-09T13:20:45Z-
dc.date.available2012-08-09T13:20:45Z-
dc.date.issued2011-03-
dc.identifier.citationTRPC6 enhances angiotensin II-induced albuminuria. 2011, 22 (3):526-35 J. Am. Soc. Nephrol.en_GB
dc.identifier.issn1533-3450-
dc.identifier.pmid21258036-
dc.identifier.doi10.1681/ASN.2010050522-
dc.identifier.urihttp://hdl.handle.net/10147/237972-
dc.description.abstractMutations in the canonical transient receptor potential cation channel 6 (TRPC6) are responsible for familial forms of adult onset focal segmental glomerulosclerosis (FSGS). The mechanisms by which TRPC6 mutations cause kidney disease are not well understood. We used TRPC6-deficient mice to examine the function of TRPC6 in the kidney. We found that adult TRPC6-deficient mice had BP and albumin excretion rates similar to wild-type animals. Glomerular histomorphology revealed no abnormalities on both light and electron microscopy. To determine whether the absence of TRPC6 would alter susceptibility to hypertension and renal injury, we infused mice with angiotensin II continuously for 28 days. Although both groups developed similar levels of hypertension, TRPC6-deficient mice had significantly less albuminuria, especially during the early phase of the infusion; this suggested that TRPC6 adversely influences the glomerular filter. We used whole-cell patch-clamp recording to measure cell-membrane currents in primary cultures of podocytes from both wild-type and TRPC6-deficient mice. In podocytes from wild-type mice, angiotensin II and a direct activator of TRPC6 both augmented cell-membrane currents; TRPC6 deficiency abrogated these increases in current magnitude. Our findings suggest that TRPC6 promotes albuminuria, perhaps by promoting angiotensin II-dependent increases in Ca(2+), suggesting that TRPC6 blockade may be therapeutically beneficial in proteinuric kidney disease.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed?term=TRPC6%20enhances%20angiotensin%20II-induced%20albuminuria.%20en_GB
dc.rightsArchived with thanks to Journal of the American Society of Nephrology : JASNen_GB
dc.subject.meshAlbuminuria-
dc.subject.meshAngiotensin II-
dc.subject.meshAnimals-
dc.subject.meshCalcium-
dc.subject.meshDisease Models, Animal-
dc.subject.meshHypertension-
dc.subject.meshInjections, Subcutaneous-
dc.subject.meshKidney-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshPatch-Clamp Techniques-
dc.subject.meshPodocytes-
dc.subject.meshTRPC Cation Channels-
dc.titleTRPC6 enhances angiotensin II-induced albuminuria.en_GB
dc.typeArticleen
dc.contributor.departmentCenter for Human Genetics, Duke University Medical Center, Durham, NC 27710, USA.en_GB
dc.identifier.journalJournal of the American Society of Nephrology : JASNen_GB
dc.description.provinceLeinsteren

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