title: Inhibition of transient receptor potential melastatin 7 (TRPM7) channel induces RA FLSs apoptosis through endoplasmic reticulum (ER) stress.
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.
authors.affiliation: School of Pharmacy, Anhui Medical University, Mei Shan Road, Hefei, Anhui Province, 230032, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wang
authors.forename: Yarui
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Huang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology; D001896:Boron Compounds / Q000494:pharmacology; D002154:Calpain / Q000378:metabolism; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005682:Gadolinium / Q000494:pharmacology; D008297:Male; D034741:RNA, Small Interfering; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D050053:TRPM Cation Channels / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism
chemical_list: D001896:Boron Compounds; C497251:Ddit3 protein, rat; D034741:RNA, Small Interfering; D050053:TRPM Cation Channels; D051742:Transcription Factor CHOP; D005682:Gadolinium; C109986:2-aminoethoxydiphenyl borate; C486584:Trpm7 protein, rat; D002154:Calpain; D053148:Caspase 3
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