School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Mei Shan Road, Hefei, 230032, Anhui, China.
Inflamm Res. 2013 Nov;62(11):961-70. doi: 10.1007/s00011-013-0653-9. Epub 2013 Aug 11.
Transient receptor potential melastatin 7 (TRPM7) is involved in both normal physiological processes and pathology of various diseases. The purpose of this study was to explore the function and underlying mechanisms of TRPM7 channels in human lung fibroblast (MRC5) proliferation and differentiation induced by transforming growth factor β1 (TGF-β1) in vitro.
We determined the expression of TRPM7 in MRC5 cells in response to TGF-β1 treatment in vitro. Chemical inhibitors (Gd(3+) and 2-APB) and specific siRNA for TRPM7 were used to study the role of TRPM7 in MRC5 cell proliferation and differentiation. The phosphorylation of Akt was determined by Western blotting.
The expression of TRPM7 was significantly potentiated in response to TGF-β1. Co-incubation of MRC5 cells with Gd(3+), 2-APB or TRPM7-siRNA decreased cell proliferation and differentiation. Furthermore, we found that suppression of TRPM7 channels also reduced the p-Akt in MRC5 cells induced by TGF-β1. We conclude that suppression of TRPM7 channels may decrease fibroblast proliferation and differentiation stimulated by TGF-β1 in vitro and this is associated with Akt phosphorylation.
瞬时受体电位 melastatin 7（TRPM7）参与多种疾病的正常生理过程和病理过程。本研究旨在探讨 TRPM7 通道在转化生长因子 β1（TGF-β1）体外诱导人肺成纤维细胞（MRC5）增殖和分化中的功能及其潜在机制。
我们测定了体外 TGF-β1 处理后 MRC5 细胞中 TRPM7 的表达。采用化学抑制剂（Gd（3+）和 2-APB）和 TRPM7 特异性 siRNA 研究 TRPM7 在 MRC5 细胞增殖和分化中的作用。采用 Western blot 法测定 Akt 的磷酸化。
TGF-β1 能显著增强 TRPM7 的表达。MRC5 细胞与 Gd（3+）、2-APB 或 TRPM7-siRNA 共同孵育可降低细胞增殖和分化。此外，我们发现抑制 TRPM7 通道也可减少 TGF-β1 诱导的 MRC5 细胞中 p-Akt。我们的结论是，抑制 TRPM7 通道可能会降低 TGF-β1 刺激的体外成纤维细胞增殖和分化，这与 Akt 磷酸化有关。
