Linked Life Data

17005937

Source:http://linkedlifedata.com/resource/pubmed/id/17005937

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-27
pubmed:abstractText
It has been shown that blockade of Rho kinase with pharmacologic inhibitors inhibits renal fibrosis. This study examined the role of Rho kinase in renal fibrosis in the unilateral ureteral obstruction (UUO) model in mice that do not express the ROCK1 gene, a critical downstream mediator of Rho GTPase. Unexpected, real-time PCR, Western blot, and immunohistochemistry demonstrated that, compared with the wild-type mice, mice with ROCK1 knockout (KO) were not protected against renal fibrosis at both the early (day 5) and late (day 10) UUO, as determined by histology and expression of both mRNA and protein levels of alpha-smooth muscle actin, collagen types I and III, and fibronectin within the diseased kidney. Then the mechanisms of loss of protective effect on renal fibrosis in ROCK1 KO mice were investigated. It is interesting that mice that lacked ROCK1 did not have altered expression of ROCK2 but significantly increased TGF-beta expression and Smad2/3 activation (phosphorylation and nuclear translocation) in the diseased kidney at day 5, which remained high at day 10 of UUO. Similarly, primary cultures of kidney fibroblasts that were obtained from both ROCK1 wild-type and KO mice showed that deletion of ROCK1 did not prevent TGF-beta-induced activation of Smad2/3 and collagen I expression. This also was observed in the presence of Rho kinase inhibitor Y-27632. Taken together, results from this study suggest that Rho/Rho kinase may not be a necessary or a central pathway for renal fibrosis in the UUO model. The interplay between the Rho/Rho kinase pathway and the Smad signaling pathway may be a key mechanism by which loss of ROCK1 does not prevent renal fibrosis in the UUO model.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1046-6673
pubmed:author
pubmed:issnType
Print
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3105-14
pubmed:dateRevised
2008-7-31
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Signaling mechanism of renal fibrosis in unilateral ureteral obstructive kidney disease in ROCK1 knockout mice.
pubmed:affiliation
Department of Medicine-Nephrology, West China Hospital of Sichuan University, Chengdu, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural