title: Regulation of fibrillar collagen-mediated smooth muscle cell proliferation in response to chemical stimuli by telomere reverse transcriptase through c-Myc.
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.
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan.
authors: Wei-Li
authors: WL
authors: Wang
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan.
authors: Yi-Ting
authors: YT
authors: Yeh
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan.
authors: Li-Jing
authors: LJ
authors: Chen
authors: Institute of Cellular and System Medicine, National Health Research Institutes, Miaoli 350, Taiwan. Electronic address: jjchiu@nhri.org.tw.
authors: Jeng-Jiann
authors: JJ
authors: Chiu
mesh_terms: D001483:Base Sequence; D049109:Cell Proliferation; D002478:Cells, Cultured; D003094:Collagen / Q000502:physiology*; D017931:DNA Primers; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D012194:RNA-Directed DNA Polymerase / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000089804:Shelterin Complex; D016615:Telomere / Q000201:enzymology*; D034501:Telomere-Binding Proteins
chemical_list: C495876:ACD protein, human; D017931:DNA Primers; D016271:Proto-Oncogene Proteins c-myc; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D003094:Collagen; D012194:RNA-Directed DNA Polymerase
keywords: Cell cycle; Fibrillar collagen; Human telomere reverse transcriptase; Smooth muscle cell; c-Myc