Angiotensin II stimulates platelet-derived growth factor-B expression in hepatic stellate cells by activating EGR-1 / 南方医科大学学报
Journal of Southern Medical University
;
(12): 963-967, 2008.
Article
in Chinese
| WPRIM
| ID: wpr-270235
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the signal transduction mechanism underlying the effects of angiotensin II (AngII) on extracellular signal-regulated kinase 1/2 (ERK1/2), early growth response-1 (EGR-1) and platelet-derived growth factor-B (PDGF-B) in hepatic stellate cells (HSCs).</p><p><b>METHODS</b>HSC-T6 cells treated with AngII for 10 or 30 min were examined for phospho-P42/44 protein expression using Western blotting. In another experiment, the cells were preincubated for 1 h in the presence of U0126 (an inhibitor of the MAPK/ERK kinase), irbesartan (an AT-1 receptor blocker), or antioxidant-N-acetylcysteine (NAC) prior to AngII exposure, and the protein expression of phospho-P42/44 and PDGF-B were measured with Western blotting. The DNA binding activity of EGR-1 was analyzed using electrophoretic gel mobility shift assay (EMSA), and the expression of PDGF-B was detected immunohistochemically.</p><p><b>RESULTS</b>AngII induced phospho-P42/44 expression in HSC-T6, which was abrogated by U0126 or irbesartan. NAC did not inhibit phospho-P42/44 expression. EMSA showed that AngII exposure of the HSC cells markedly increased EGR-1 DNA binding activity, reaching the maximum after 60 min of exposure followed by progressive declination; irbesartan and U0126 significantly suppressed AngII-induced EGR-1 activity enhancement. ACEI at 1 micromol/L and 10 nmol/L inhibited EGR-1 activity, but ACEI at the concentration of 0.1 nmol/L resulted in enhanced EGR-1 activity. NAC showed no obvious effect in suppressing EGR-1 activity. AngII increased PDGF-B protein level in the HSCs, the effect of which was inhibited by irbesartan. U0126, NAC and ACEI did not attenuate PDGF-BB protein level in the HSCs.</p><p><b>CONCLUSION</b>Stimulation of the HSCs with AngII results in EGR-1 activation via the ERK1/2 pathway, leading to up-regulation of PDGF-B expression.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pharmacology
/
Platelet-Derived Growth Factor
/
Angiotensin II
/
Immunohistochemistry
/
Signal Transduction
/
Cells, Cultured
/
Blotting, Western
/
Proto-Oncogene Proteins c-sis
/
Cell Biology
/
Extracellular Signal-Regulated MAP Kinases
Limits:
Humans
Language:
Chinese
Journal:
Journal of Southern Medical University
Year:
2008
Type:
Article
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