Knockdown of TRPM۷ attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-۶ via modulating TLR۴/NF-κB and MEK/ERK pathways
Publish place: Iranian Journal of Basic Medical Sciences، Vol: 25، Issue: 8
Publish Year: 1401
نوع سند: مقاله ژورنالی
زبان: English
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JR_IJBMS-25-8_003
تاریخ نمایه سازی: 31 مرداد 1401
Abstract:
Objective(s): Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal critical illness in neonatal infants. TRPM۷ reportedly plays a role in human inflammatory bowel disease (IBD) and colorectal cancer, but the role of TRPM۷ in the pathogenesis of NEC remains vague.Materials and Methods: The expression of TRPM۷ was determined in intestinal tissues of NEC patients and lipopolysaccharide (LPS)-induced IEC-۶ cells. Subsequently, a loss-of-function assay was performed to assess the effects of TRPM۷ on cell apoptosis and inflammatory response in IEC-۶ cells after LPS induction. Furthermore, the modulation of TRPM۷ on TLR۴/NF-κB and MEK/ERK signaling pathways was validated.Results: The expression of TRPM۷ was higher in the intestinal tissues of NEC patients compared with the normal human intestinal tissues. Moreover, the expression level of TRPM۷ was elevated in LPS stimulation IEC-۶ cells. Knockdown of TRPM۷ enhanced cell viability and suppressed apoptosis, accompanied by the decreased Bax/Bcl-۱ ratio and cleaved-caspase۳ expression in LPS-induced IEC-۶ cells. Additionally, TRPM۷ silencing attenuated LPS-induced expressions and secretions of proinflammatory cytokines. Mechanistically, TRPM۷ knockdown inhibited the TLR۴/NF-κB activation, while enhancing the MEK/ERK activation in LPS-treated IEC-۶ cells. Overexpression of TLR۴ or inhibition of MEK attenuated the inhibitory effects of TRPM۷ knockdown on LPS-induced apoptosis and inflammation in IEC-۶ cells.Conclusion: Knockdown of TRPM۷ attenuated LPS-induced IEC-۶ cell apoptosis and inflammation by modulating TLR۴/NF-κB and MEK/ERK pathways.
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Authors
Qi Wang
The Affiliated Children Hospital of Xi’an Jiaotong University
Lu An
Department of Pathology,xi&#۰۳۹;an Chlidren&#۰۳۹;s Hospital
Juan Li
Department of Pathology,xi&#۰۳۹;an Chlidrend&#۰۳۹;s Hospital
Bing Liu
Department of Patholoqy,xi&#۰۳۹;an Chlidrend&#۰۳۹;s Hospital
Junpeng Hui
Department of Pathology,xi&#۰۳۹;an Chlidrend&#۰۳۹;s Hospital
Qiang Zhang
Department of Pathology,xi&#۰۳۹;an Chlidrend&#۰۳۹;s Hospital
Xin Zhang
Department of Pathology,xi&#۰۳۹;an Chlidrend&#۰۳۹;s Hospital