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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-5-25
pubmed:abstractText
The present study investigated whether transforming growth factor-beta 1 (TGF-beta1) exerts an autocrine positive effect on angiotensinogen (ANG) gene expression in rat kidney proximal tubular cells, and delineates its underlying mechanism(s) of action. Rat immortalized renal proximal tubular cells (IRPTCs) and freshly isolated mouse renal proximal tubules were incubated in the absence or presence of active human TGF-beta1. IRPTCs were also stably transfected with rat TGF-beta1 or p53 tumor suppressor protein (p53) cDNA in sense (S) and antisense (AS) orientations. ANG mRNA and p53 protein expression were assessed by reverse transcription-polymerase chain reaction and Western blotting, respectively. Reactive oxygen species (ROS) generation was quantified by lucigenin assay. Active TGF-beta1 evoked ROS generation and stimulated ANG mRNA and p53 protein expression, whereas a superoxide scavenger and inhibitors of nicotinamide adenine dinucleotide oxidase and p38 mitogen-activated protein kinase (p38 MAPK) abolished the TGF-beta1 effect. Stable transfer of p53 cDNA (S) enhanced and p53 cDNA (AS) abolished the stimulatory effect of TGF-beta1 on ANG mRNA expression in IRPTCs. Our results demonstrate that TGF-beta1 stimulates ANG gene expression and its action is mediated, at least in part, via ROS generation, p38 MAPK activation, and p53 expression, suggesting that angiotensin II and TGF-beta1 may form a positive feedback loop to enhance their respective gene expression, leading to renal injury.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
69
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1977-85
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Transforming growth factor-beta 1 stimulates angiotensinogen gene expression in kidney proximal tubular cells.
pubmed:affiliation
Centre de recherche, Centre hospitalier de l'Université de Montréal-Hôtel-Dieu, Pavillon Masson, Montreal, Quebec, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural