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Basic fibroblast growth factor decreases elastin gene transcription in aortic smooth muscle cells
Author(s) -
Carreras Isabel,
Rich Celeste B.,
Panchenko Mikhail P.,
Foster Judith Ann
Publication year - 2002
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.10163
Subject(s) - elastin , tropoelastin , basic fibroblast growth factor , ap 1 transcription factor , microbiology and biotechnology , extracellular matrix , downregulation and upregulation , vascular smooth muscle , gene expression , biology , transcription factor , chemistry , gene , growth factor , endocrinology , biochemistry , smooth muscle , receptor , genetics
The extracellular matrix (ECM) protein elastin plays an essential role in the cardiovascular system by imparting elasticity to blood vessel wall. In this study, we examined the effect of basic fibroblast growth factor (bFGF) on the expression of elastin in aortic smooth muscle cells (SMC) to gain insight into events associated with cardiovascular diseases. The results show that bFGF treatment of SMC causes a significant decrease in elastin mRNA and secreted tropoelastin levels. Nuclear run‐on analyses demonstrate that the downregulation is due to a decrease in the level of elastin gene transcription. Transient transfections of SMC with wild‐type and mutated elastin gene promoter/chloramphenicol acetyl transferase (CAT) constructs show that a previously identified activator protein‐1‐cAMP response element (AP1/CRE) (−564 to −558‐bp) within the elastin promoter mediates the bFGF‐dependent downregulation of elastin gene transcription in SMC. Addition of bFGF to SMC activates the extracellular signal‐regulated kinases 1/2 (ERK1/2) resulting in their translocation into the nucleus and subsequent induction of Fra‐1. The addition of PD‐98059, an inhibitor of ERK1/2 kinase, abrogates the bFGF‐dependent decrease of elastin mRNA in SMC. The described inhibitory effect of bFGF on elastin gene expression in SMC may significantly contribute to the inefficient repair of elastin in early stages of vascular wall injury. J. Cell. Biochem. 85: 592–600, 2002. © 2002 Wiley‐Liss, Inc.