Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways
Objective(s): Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal critical illness in neonatal infants. TRPM7 reportedly plays a role in human inflammatory bowel disease (IBD) and colorectal cancer, but the role of TRPM7 in the pathogenesis of NEC remains vague.Materials and...
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| Format: | Article |
| Language: | English |
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Mashhad University of Medical Sciences
2022-08-01
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| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_20669_29e5c6e8bdc69a0405583ce833702619.pdf |
| _version_ | 1811192555053776896 |
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| author | Qi Wang Lu An Juan Li Bing Liu Junpeng Hui Qiang Zhang Xin Zhang |
| author_facet | Qi Wang Lu An Juan Li Bing Liu Junpeng Hui Qiang Zhang Xin Zhang |
| author_sort | Qi Wang |
| collection | DOAJ |
| description | Objective(s): Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal critical illness in neonatal infants. TRPM7 reportedly plays a role in human inflammatory bowel disease (IBD) and colorectal cancer, but the role of TRPM7 in the pathogenesis of NEC remains vague.Materials and Methods: The expression of TRPM7 was determined in intestinal tissues of NEC patients and lipopolysaccharide (LPS)-induced IEC-6 cells. Subsequently, a loss-of-function assay was performed to assess the effects of TRPM7 on cell apoptosis and inflammatory response in IEC-6 cells after LPS induction. Furthermore, the modulation of TRPM7 on TLR4/NF-κB and MEK/ERK signaling pathways was validated.Results: The expression of TRPM7 was higher in the intestinal tissues of NEC patients compared with the normal human intestinal tissues. Moreover, the expression level of TRPM7 was elevated in LPS stimulation IEC-6 cells. Knockdown of TRPM7 enhanced cell viability and suppressed apoptosis, accompanied by the decreased Bax/Bcl-1 ratio and cleaved-caspase3 expression in LPS-induced IEC-6 cells. Additionally, TRPM7 silencing attenuated LPS-induced expressions and secretions of proinflammatory cytokines. Mechanistically, TRPM7 knockdown inhibited the TLR4/NF-κB activation, while enhancing the MEK/ERK activation in LPS-treated IEC-6 cells. Overexpression of TLR4 or inhibition of MEK attenuated the inhibitory effects of TRPM7 knockdown on LPS-induced apoptosis and inflammation in IEC-6 cells.Conclusion: Knockdown of TRPM7 attenuated LPS-induced IEC-6 cell apoptosis and inflammation by modulating TLR4/NF-κB and MEK/ERK pathways. |
| first_indexed | 2024-04-11T23:54:33Z |
| format | Article |
| id | doaj.art-e382c691f4a1477f9b083e3f74494115 |
| institution | Directory Open Access Journal |
| issn | 2008-3866 2008-3874 |
| language | English |
| last_indexed | 2024-04-11T23:54:33Z |
| publishDate | 2022-08-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj.art-e382c691f4a1477f9b083e3f744941152022-12-22T03:56:24ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742022-08-0125894795310.22038/ijbms.2022.62113.1374220669Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathwaysQi Wang0Lu An1Juan Li2Bing Liu3Junpeng Hui4Qiang Zhang5Xin Zhang6The Affiliated Children Hospital of Xi’an Jiaotong UniversityDepartment of Pathology,xi'an Chlidren's HospitalDepartment of Pathology,xi'an Chlidrend's HospitalDepartment of Patholoqy,xi'an Chlidrend's HospitalDepartment of Pathology,xi'an Chlidrend's HospitalDepartment of Pathology,xi'an Chlidrend's HospitalDepartment of Pathology,xi'an Chlidrend's HospitalObjective(s): Neonatal necrotizing enterocolitis (NEC) is the most common gastrointestinal critical illness in neonatal infants. TRPM7 reportedly plays a role in human inflammatory bowel disease (IBD) and colorectal cancer, but the role of TRPM7 in the pathogenesis of NEC remains vague.Materials and Methods: The expression of TRPM7 was determined in intestinal tissues of NEC patients and lipopolysaccharide (LPS)-induced IEC-6 cells. Subsequently, a loss-of-function assay was performed to assess the effects of TRPM7 on cell apoptosis and inflammatory response in IEC-6 cells after LPS induction. Furthermore, the modulation of TRPM7 on TLR4/NF-κB and MEK/ERK signaling pathways was validated.Results: The expression of TRPM7 was higher in the intestinal tissues of NEC patients compared with the normal human intestinal tissues. Moreover, the expression level of TRPM7 was elevated in LPS stimulation IEC-6 cells. Knockdown of TRPM7 enhanced cell viability and suppressed apoptosis, accompanied by the decreased Bax/Bcl-1 ratio and cleaved-caspase3 expression in LPS-induced IEC-6 cells. Additionally, TRPM7 silencing attenuated LPS-induced expressions and secretions of proinflammatory cytokines. Mechanistically, TRPM7 knockdown inhibited the TLR4/NF-κB activation, while enhancing the MEK/ERK activation in LPS-treated IEC-6 cells. Overexpression of TLR4 or inhibition of MEK attenuated the inhibitory effects of TRPM7 knockdown on LPS-induced apoptosis and inflammation in IEC-6 cells.Conclusion: Knockdown of TRPM7 attenuated LPS-induced IEC-6 cell apoptosis and inflammation by modulating TLR4/NF-κB and MEK/ERK pathways.https://ijbms.mums.ac.ir/article_20669_29e5c6e8bdc69a0405583ce833702619.pdfapoptosisinflammationnecrotizing enterocolitistrpm7viability |
| spellingShingle | Qi Wang Lu An Juan Li Bing Liu Junpeng Hui Qiang Zhang Xin Zhang Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways Iranian Journal of Basic Medical Sciences apoptosis inflammation necrotizing enterocolitis trpm7 viability |
| title | Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways |
| title_full | Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways |
| title_fullStr | Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways |
| title_full_unstemmed | Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways |
| title_short | Knockdown of TRPM7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell IEC-6 via modulating TLR4/NF-κB and MEK/ERK pathways |
| title_sort | knockdown of trpm7 attenuates apoptosis and inflammation in neonatal necrotizing enterocolitis model cell iec 6 via modulating tlr4 nf κb and mek erk pathways |
| topic | apoptosis inflammation necrotizing enterocolitis trpm7 viability |
| url | https://ijbms.mums.ac.ir/article_20669_29e5c6e8bdc69a0405583ce833702619.pdf |
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