Article ; Online: Inhibition of transient receptor potential melastatin 7 (TRPM7) channel induces RA FLSs apoptosis through endoplasmic reticulum (ER) stress.
2014 Volume 33, Issue 11, Page(s) 1565–1574
Abstract: ... stress. Therefore, inhibition of TRPM7 could activate ER stress and induce RA FLSs apoptosis. ... Transient receptor potential melastatin 7 (TRPM7) is involved in both normal ... channels may increase RA FLSs apoptosis in vitro, and this is associated with endoplasmic reticulum (ER ...
| Abstract | 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 rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLSs) apoptosis induced by thapsigargin in vitro. In this study, using a combination of Western blotting, RT-PCR, and nuclear morphology analysis, we investigated the influence and potential function of TRPM7 channels on the apoptosis induced by thapsigargin in RA FLSs. Chemical inhibitors (Gd(3+) and 2-APB) and specific siRNA for TRPM7 were used to study the role of TRPM7 in RA FLSs apoptosis. The expression of TRPM7 was significantly potentiated in RA FLSs. Co-incubation of RA FLSs with Gd(3+), 2-APB, or TRPM7-siRNA increased cell apoptosis. Furthermore, we found that suppression of TRPM7 channels also increased the expression CHOP and calpain and decreased the expression caspase-3. We conclude that suppression of TRPM7 channels may increase RA FLSs apoptosis in vitro, and this is associated with endoplasmic reticulum (ER) stress. Therefore, inhibition of TRPM7 could activate ER stress and induce RA FLSs apoptosis. |
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| MeSH term(s) | Animals ; Apoptosis/drug effects ; Arthritis, Rheumatoid/metabolism ; Arthritis, Rheumatoid/pathology ; Boron Compounds/pharmacology ; Calpain/metabolism ; Caspase 3/metabolism ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects ; Fibroblasts/drug effects ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Gadolinium/pharmacology ; Male ; RNA, Small Interfering ; Rats ; Rats, Sprague-Dawley ; Synovial Membrane/drug effects ; Synovial Membrane/metabolism ; Synovial Membrane/pathology ; TRPM Cation Channels/antagonists & inhibitors ; TRPM Cation Channels/genetics ; TRPM Cation Channels/metabolism ; Transcription Factor CHOP/metabolism | |||||
| Chemical Substances | Boron Compounds ; Ddit3 protein, rat ; RNA, Small Interfering ; TRPM Cation Channels ; Transcription Factor CHOP (147336-12-7) ; Gadolinium (AU0V1LM3JT) ; 2-aminoethoxydiphenyl borate (E4ES684O93) ; Trpm7 protein, rat (EC 2.7.11.1) ; Calpain (EC 3.4.22.-) ; Caspase 3 (EC 3.4.22.-) | |||||
| Language | English | |||||
| Publishing date | 2014-04-15 | |||||
| Publishing country | Germany | |||||
| Document type | Journal Article ; Research Support, Non-U.S. Gov't | |||||
| ZDB-ID | 604755-5 | |||||
| ISSN | 1434-9949 ; 0770-3198 | |||||
| ISSN (online) | 1434-9949 | |||||
| ISSN | 0770-3198 | |||||
| DOI | 10.1007/s10067-014-2599-x | |||||
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| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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