Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
Cell Biochem Funct. 2011 Jan-Feb;29(1):64-70. doi: 10.1002/cbf.1720.
Epidermal growth factor (EGF) promotes proliferation in human mesenchymal stem cells (hMSCs) during in vitro propagation. In this study, we investigated the effects of PI3K/AKT, ERK1/2, P38 and JNK on EGF signalling in hMSCs. The effects of EGF on MAPKs and PI3K/AKT crosstalk were investigated by immunoblotting; cyclooxygenase-2 (COX-2) expression was studied by real-time RT-PCR; and cell proliferation was evaluated by methylthiazolyl tetrazolium bromide assay. Our results showed that EGF immediately activated all four pathways, induced proliferation and increased COX-2 expression. Interestingly, inhibition of PI3K/AKT-enhanced EGF-stimulated ERK1/2 activity, and inhibition of ERK1/2 and JNK reduced AKT phosphorylation. Furthermore, EGF-induced proliferation as well as EGF-augmented COX2 expression was hindered by ERK1/2 and p38 inhibitors. The results of this study provide evidences to be used in extended proliferation of hMSCs for cell therapy.
表皮生长因子 (EGF) 在人骨髓间充质干细胞 (hMSCs) 的体外扩增过程中促进其增殖。在这项研究中，我们研究了 PI3K/AKT、ERK1/2、P38 和 JNK 对 hMSCs 中 EGF 信号的影响。通过免疫印迹研究了 EGF 对 MAPKs 和 PI3K/AKT 串扰的影响；通过实时 RT-PCR 研究了环氧化酶-2 (COX-2) 的表达；通过噻唑蓝溴化盐比色法评估细胞增殖。结果表明，EGF 立即激活了这四条通路，诱导了细胞增殖并增加了 COX-2 的表达。有趣的是，PI3K/AKT 的抑制增强了 EGF 刺激的 ERK1/2 活性，而 ERK1/2 和 JNK 的抑制降低了 AKT 的磷酸化。此外，ERK1/2 和 p38 抑制剂阻碍了 EGF 诱导的增殖和 EGF 增强的 COX2 表达。这项研究的结果为细胞治疗中 hMSCs 的扩展增殖提供了证据。
