Calcitonin gene-related peptide regulates mitogen-activated protein kinase pathway to decrease transforming growth factor ß1-induced hepatic plasminogen activator inhibitor-1 mRNA expression in HepG2 cells.
Biosci Biotechnol Biochem
; 78(5): 787-90, 2014.
Article
in En
| MEDLINE
| ID: mdl-25035980
ABSTRACT
Transforming growth factor (TGF) ß1-induced plasminogen activator inhibitor (PAI)-1 is one of factors associated with the development of hepatic fibrosis. Calcitonin gene-related peptide (CGRP) shows hepatoprotective effect during hepatic injuries, including fibrosis. However, the effects of CGRP on PAI-1 expression induced by TGFß1 are unknown. In this study, we investigated the effect of CGRP on TGFß1-induced PAI-1 expression and its regulatory mechanisms in HepG2 cells. CGRP inhibited TGFß1-induced PAI-1 expression. H89, a protein kinase A inhibitor, abolished the inhibition of TGFß1-induced PAI-1 expression by CGRP. TGFß1 activated mitogen-activated protein kinase (MAPK), including extracellular signal-regulated kinase, c-jun NH2-terminal kinase, and p38, and this activation was abolished by CGRP. These results show that the CGRP-induced cAMP/PKA activation suppresses activation of MAPK induced by TGFß1, leading to decreased PAI-1 expression in HepG2 cells.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcitonin Gene-Related Peptide
/
Gene Expression Regulation
/
Plasminogen Activator Inhibitor 1
/
Mitogen-Activated Protein Kinases
/
MAP Kinase Signaling System
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Transforming Growth Factor beta1
/
Liver
Limits:
Humans
Language:
En
Journal:
Biosci Biotechnol Biochem
Journal subject:
BIOQUIMICA
/
BIOTECNOLOGIA
Year:
2014
Document type:
Article
Affiliation country: