Linked Life Data

21048023

Source:http://linkedlifedata.com/resource/pubmed/id/21048023

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-7
pubmed:abstractText
Increased mechanical load in podocytes due to glomerular hypertension is one of the important factors leading to podocyte damage and chronic kidney disease. In previous studies, we have shown that mechanical stretch increases osteopontin (OPN) expression in podocytes and that exogenous OPN is mechanoprotective via facilitating cytoskeletal reorganization of podocytes. In the present study, we asked whether the mechanoprotective effect of OPN in podocytes is mediated through specific integrins and whether endogenous OPN of podocytes is required for mechanoprotection. Conditionally immortalized mouse podocytes and primary podocytes (PP) from OPN-/- and OPN+/+ mice were used. Cyclic biaxial mechanical stretch (0.5 Hz, 7% linear strain) was applied for up to 3 days. Stretch-induced cell loss was ?30% higher in OPN-/- PP compared with OPN+/+ PP. Increased cell loss of OPN-/- PP was rescued by OPN coating. Analysis of integrin expression by RT-PCR, application of RGD and SLAYGLR peptides and anti-integrin antibodies, small-interfering RNA knockdown of integrins, and application of kinase inhibitors identified ?V-integrins (?V?1, ?V?3, and ?V?5) to mediate the mechano-protective effect of OPN in podocytes involving focal adhesion kinase, Src, phosphatidylinositol 3-kinase, and mitogen-activated protein kinase. Our results demonstrate that endogenous OPN of podocytes plays a nonredundant role in podocyte adaptation to mechanical stretch, and that OPN signaling via ?(V)-integrins may represent a relevant therapeutical target in podocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1522-1466
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
300
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F119-32
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
AlphaV-integrins mediate the mechanoprotective action of osteopontin in podocytes.
pubmed:affiliation
Department of Anatomy and Cell Biology, University of Greifswald, Greifswald, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't