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Biomaterials. 2014 Apr;35(12):3829-39. doi: 10.1016/j.biomaterials.2014.01.049. Epub 2014 Feb 5.

Regulation of fibrillar collagen-mediated smooth muscle cell proliferation in response to chemical stimuli by telomere reverse transcriptase through c-Myc.

Author information

1
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan.
2
Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan. Electronic address: jjchiu@nhri.org.tw.

Abstract

Human telomerase reverse transcriptase (hTERT) and oncogene c-Myc have been shown to regulate cell proliferation. Our previous studies demonstrated that fibrillar collagen mediates vascular smooth muscle cell (SMC) cycle progression and proliferation in response to platelet-derived growth factor (PDGF)-BB and interleukin (IL)-1β. However, whether hTERT and c-Myc are involved in these fibrillar collagen-mediated SMC responses remain unclear. The present study elucidated the regulatory role of hTERT and c-Myc in PDGF-BB/IL-1β-induced cell cycle progression in SMCs on fibrillar collagen and its underlying mechanisms. Our results showed that PDGF-BB and IL-1β exert synergistic effects to induce hTERT expression, but not its activity, in human arterial SMCs on fibrillar collagen. This PDGF-BB/IL-1β-induced up-regulation of hTERT contributes to cell cycle progression in SMCs through the up-regulation of cyclin-dependent kinase-6 and down-regulations of p27(KIP1) and p21(CIP1). In addition, PDGF-BB/IL-1β induces up-regulation of c-Myc in SMCs on fibrillar collagen; this response is mediated by the increased binding of hTERT, which can form complexes with TPP1 and hnRNPK, to the guanine-rich region of the c-Myc promoter and consequently contributes to cell cycle progression in SMCs on fibrillar collagen. Moreover, the PDGF-BB/IL-1β-induced hTERT and c-Myc expressions are regulated by phosphatidylinositol 3-kinase/Akt in SMCs on fibrillar collagen. Our findings provide insights into the mechanisms by which hTERT and c-Myc regulates SMC cell cycle progression and proliferation on fibrillar collagen in response to chemical stimuli.

KEYWORDS:

Cell cycle; Fibrillar collagen; Human telomere reverse transcriptase; Smooth muscle cell; c-Myc

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