Epidermal growth factor up-regulates the expression of nestin through the Ras-Raf-ERK signaling axis in rat vascular smooth muscle cells.
The contractile-synthetic phenotypic modulation of vascular smooth muscle cells (VSMCs) is a key event during atherosclerosis progression. Although many studies have reported possible cytokines and growth factors implicated to this process, the critical factors affecting the VSMC phenotype remain unclear due to the lack of early de-differentiation marker identifications. In this study, we showed that nestin, an intermediate filament protein, is expressed in primary cultures of rat VSMCs representing the synthetic phenotype and its expression is diminished as these cells re-differentiate after serum deprivation. However, the regulation of nestin expression was never reported despite its common usage as an early differentiation marker. Herein, we showed that nestin expression is regulated by epidermal growth factor (EGF) via de novo RNA and protein synthesis. Furthermore, signaling analyses revealed that the EGF-induced nestin re-expression is mediated through the activation of the Ras-Raf-ERK signaling axis. This is the first report to show that nestin expression is regulated by an extracellular signaling molecule.
Institute of Molecular and Cellular Biology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
Yuan-Li
YL
Huang
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan; Cardiovascular Research Center, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan.
Guey-Yueh
GY
Shi
Department of Cell Biology and Anatomy, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan.
Meei-Jyh
MJ
Jiang
Institute of Zoology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
Hsinyu
H
Lee
Institute of Molecular and Cellular Biology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan.
Yao-Wen
YW
Chou
Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan; Cardiovascular Research Center, National Cheng Kung University, No. 1, University Road, Tainan 701, Taiwan.
Hua-Lin
HL
Wu
Institute of Molecular and Cellular Biology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 106, Taiwan. Electronic address: hyhy@ntu.edu.tw.
Hsi-Yuan
HY
Yang
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology / Q000502:physiology*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000096:biosynthesis* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D064231:Nestin; D014176:Protein Biosynthesis / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D048490:raf Kinases / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
D016895:Culture Media, Serum-Free; D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577486:Nes protein, rat; D064231:Nestin; D004815:Epidermal Growth Factor; D048490:raf Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins