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Article ; Online: Inhibition of TRPM7 channels prevents proliferation and differentiation of human lung fibroblasts.

Yu, Mingzhe / Huang, Cheng / Huang, Yan / Wu, Xiaoqin / Li, Xiaohui / Li, Jun

Inflammation research : official journal of the European Histamine Research Society ... [et al.

2013  Volume 62, Issue 11, Page(s) 961–970

Abstract: ... underlying mechanisms of TRPM7 channels in human lung fibroblast (MRC5) proliferation and differentiation ... that suppression of TRPM7 channels may decrease fibroblast proliferation and differentiation stimulated by TGF-β1 ... APB or TRPM7-siRNA decreased cell proliferation and differentiation. Furthermore, we found ...

Abstract 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.
Materials and 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.
MeSH term(s) Cell Cycle/drug effects ; Cell Differentiation/drug effects ; Cell Line ; Cell Proliferation/drug effects ; Fibroblasts/cytology ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Gene Silencing ; Humans ; Lung/cytology ; MCF-7 Cells ; Phosphatidylinositol 3-Kinases/metabolism ; Protein-Serine-Threonine Kinases ; Proto-Oncogene Proteins c-akt/metabolism ; RNA, Small Interfering/genetics ; TRPM Cation Channels/antagonists & inhibitors ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Transforming Growth Factor beta1/pharmacology
Chemical Substances RNA, Small Interfering ; TRPM Cation Channels ; Transforming Growth Factor beta1 ; Phosphatidylinositol 3-Kinases (EC 2.7.1.-) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; TRPM7 protein, human (EC 2.7.11.1)
Language English
Publishing date 2013-08-11
Publishing country Switzerland
Document type Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID 1221794-3
ISSN 1420-908X ; 1023-3830
ISSN (online) 1420-908X
ISSN 1023-3830
DOI 10.1007/s00011-013-0653-9
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