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Expression of Concern: High glucose facilitates cell cycle arrest of rat bone marrow multipotent adult progenitor cells through transforming growth factor‐ β 1 and extracellular signal‐regulated kinase 1/2 signalling without changing O ct4 expression
Author(s) -
Luo Min,
Liu Zehao,
Hao Hong,
Lu Tiewei,
Chen Minjie,
Lei Minxiang,
Verfaillie Catherine M,
Liu Zhenguo
Publication year - 2012
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.2012.05747.x
Subject(s) - cell cycle , biology , progenitor cell , microbiology and biotechnology , protein kinase b , cell growth , growth factor , transforming growth factor , stem cell , phosphorylation , cell , biochemistry , receptor
Summary The transcription factor O ct4 is critical to the pluripotency, self‐renewal and differentiation of stem cells. The aim of the present study was to investigate the effects of high glucose ( HG ) on the cell cycle progression of bone marrow multipotent adult progenitor cells ( MAPC ) and O ct4 expression, as well as the underlying mechanisms. Rat MAPC were cultured in normal (5.5 mmol/L d ‐glucose) and HG (25.5 mmol/L d ‐glucose) media for up to 14 days. l ‐ G lucose served as a high osmolarity control. Culture in HG media substantially increased the number of cells in the G 0 / G 1 phase and decreased the number in the S phase without changing the cell population in the G 2 phase. Expression of the cell cycle regulatory protein p21 CIP / WAF ‐1 (p21), but not that of p27 KIP ‐1 (p27), was significantly upregulated in cells cultured in HG media. Significant increases were seen in transforming growth factor ( TGF )‐β1 levels in cells and MAPC ‐conditioned medium in the presence of HG , and extracellular signal‐regulated kinase ( ERK ) 1/2 phosphorylation was enhanced in cells cultured in the presence of HG medium without any changes in A kt phosphorylation. Neutralizing TGF ‐β1 antibody effectively prevented HG ‐induced increases in ERK 1/2 phosphorylation, p21 expression and suppression of cell cycle progression of MAPC . Inhibiting ERK 1/2 phosphorylation with PD 98059 completely blocked HG ‐induced p21 expression and markedly reversed HG ‐induced inhibition of cell cycle progression in MAPC . The HG ‐induced suppression of cell cycle progression was not accompanied by inhibition of cell proliferation or O ct4 expression in these cells. The data indicate that HG facilitates cell cycle arrest of rat MAPC through TGF ‐β1‐induced activation of ERK 1/2 signalling and p21 expression, and that O ct4 expression in MAPC is independent of the cell cycle and/or TGF ‐β1 or ERK 1/2 signalling in HG medium.