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The mechanism of hydralazine-induced collagen biosynthesis in cultured fibroblasts.
MedLine Citation:
PMID:  23344524     Owner:  NLM     Status:  Publisher    
The finding that hydralazine (HYD) affects collagen metabolism led us to investigate the mechanism of its action on collagen biosynthesis, prolidase expression and activity, expression of α(2)β(1) integrin, insulin-like growth factor-I receptor (IGF-IR), focal adhesion kinase (FAK), mitogen-activated protein (MAP) kinases (ERK(1), ERK(2)), and transcription factors hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-κB p65 (NF-κB p65) in human dermal fibroblasts. Confluent fibroblasts were treated with micromolar concentrations (50-500 μM) of HYD for 24 h. HYD had no influence on cell viability. It was found that HYD-dependent increase in collagen biosynthesis was accompanied by a parallel increase in prolidase activity and expression, HIF-1α expression, and decrease in DNA biosynthesis, compared to untreated cells. Since collagen biosynthesis and prolidase activity are regulated by a signal induced by activated α(2)β(1) integrin receptor as well as IGF-IR, the expression of these receptors was measured by Western immunoblot analysis. The exposure of the cells to HYD contributed to the increase in IGF-IR expression without any effect on α(2)β(1) integrin receptor and FAK expressions. It was accompanied by a decrease in expression of MAP kinases and NF-κB p65, the known inhibitor of collagen gene expression. The data suggest that the HYD-dependent increase of collagen biosynthesis in cultured human skin fibroblasts results from activation of IGF-IR expression and prolidase activity and downregulation of NF-κB p65.
Ewa Karna; Lukasz Szoka; Jerzy A Palka
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-24
Journal Detail:
Title:  Naunyn-Schmiedeberg's archives of pharmacology     Volume:  -     ISSN:  1432-1912     ISO Abbreviation:  Naunyn Schmiedebergs Arch. Pharmacol.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0326264     Medline TA:  Naunyn Schmiedebergs Arch Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Department of Medicinal Chemistry, Medical University of Bialystok, Mickiewicza 2 D, 15-222, Bialystok, Poland.
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