Inhibition of TRPM7 channels prevents proliferation and differentiation of human lung fibroblasts.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.
School of Pharmacy, Anhui Key Laboratory of Bioactivity of Natural Products, Anhui Medical University, Mei Shan Road, Hefei, 230032, Anhui, China.
Mingzhe
M
Yu
Cheng
C
Huang
Yan
Y
Huang
Xiaoqin
X
Wu
Xiaohui
X
Li
Jun
J
Li
D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020868:Gene Silencing; D006801:Humans; D008168:Lung / Q000166:cytology; D061986:MCF-7 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; D053773:Transforming Growth Factor beta1; C486583:TRPM7 protein, human