Source:http://linkedlifedata.com/resource/pubmed/id/20438519
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2010-5-4
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pubmed:abstractText |
15-Deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) is an endogenous peroxisome proliferator-activated receptor gamma (PPARgamma) agonist that suppresses progressive matrix deposition; however, little is known about the effects of 15d-PGJ(2) on human peritoneal mesothelial cells (HPMCs). We investigated the following: (i) the expression of PPARgamma; (ii) the effect of 15d-PGJ(2) on angiotensin II (Ang II)-induced fibronectin (FN) expression and secretion; (iii) the effect of 15d-PGJ(2) (with or without Ang II and with or without the specific PPARgamma antagonist GW9662) and pioglitazone, a synthetic PPARgamma agonist, on hepatocyte growth factor (HGF) expression and secretion; (iv) the effect of HGF on Ang II-induced FN expression and secretion; (v) the expression of c-Met (a specific HGF receptor) and its phospho-signal; and (vi) the involvement of HGF in the effect produced by 15d-PGJ(2) using selective c-Met inhibitor PHA-665752. The presence of PPARgamma was detected by western blot analysis. 15d-PGJ(2) inhibited Ang II-induced FN expression and increased HGF expression, even in the presence of Ang II. This effect of HGF expression was completely prevented by co-treatment with GW9662. Additionally, upregulation of HGF secretion induced by 15d-PGJ(2) and HGF production induced by pioglitazone was revealed. We demonstrated the presence of c-Met, and presented evidence that HGF inhibits Ang II-induced FN expression and activates phosphorylation of c-Met, which is blocked by PHA-665752; 15d-PGJ(2) also activated c-Met phosphorylation. Furthermore, PHA-665752 attenuates the inhibitory effects of 15d-PGJ(2) on FN secretion. These findings suggest that 15d-PGJ(2) has a novel and potent antifibrotic effect in HPMC and this action is likely mediated by HGF.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/15-deoxy-delta(12,14)-prostaglandin...,
http://linkedlifedata.com/resource/pubmed/chemical/Angiotensin II,
http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Immunologic Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Prostaglandin D2
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1744-9987
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
43-51
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pubmed:meshHeading |
pubmed-meshheading:20438519-Analysis of Variance,
pubmed-meshheading:20438519-Angiotensin II,
pubmed-meshheading:20438519-Blotting, Western,
pubmed-meshheading:20438519-Cells, Cultured,
pubmed-meshheading:20438519-Epithelium,
pubmed-meshheading:20438519-Fibronectins,
pubmed-meshheading:20438519-Hepatocyte Growth Factor,
pubmed-meshheading:20438519-Humans,
pubmed-meshheading:20438519-Immunologic Factors,
pubmed-meshheading:20438519-Peritoneum,
pubmed-meshheading:20438519-Prostaglandin D2,
pubmed-meshheading:20438519-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20438519-Up-Regulation
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pubmed:year |
2010
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pubmed:articleTitle |
15-Deoxy-Delta12,14-prostaglandin J2 inhibits angiotensin II-induced fibronectin expression via hepatocyte growth factor induction in human peritoneal mesothelial cells.
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pubmed:affiliation |
Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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