Dexmedetomidine reduces dextran sulfate sodium (DSS)-induced NCM460 cell inflammation and barrier damage by inhibiting RhoA/ROCK signaling pathway
Main Article Content
Keywords
dexmedetomidine, inflammation, barrier damage, RhoA/ROCK signaling pathway, ulcerative colitis
Abstract
Objective: This study investigated the role of dexmedetomidine (DEX) in dextran sulfate sodium (DSS)-induced NCM460 cells.
Material and Methods: The viability and apoptosis of NCM460 cells treated with DEX with or without DSS were detected by CCK-8 and terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay. The level of inflammatory factors and expression of inflammation-related proteins, tight junction proteins and Ras homolog gene family, member A/Rho-associated coiled-coil containing protein kinase (RhoA/ROCK) signaling-related proteins in NCM460 cells treated with DEX and/or U46619 (RhoA/ROCK agonist) and/or DSS were detected by the respective enzyme-linked immunosorbent assay (ELISA) kits and Western blot analysis. The permeability of NCM460 monolayers was examined with transepithelial electrical resistance (TEER) assay.
Results: DEX had no effect on NCM460 cell viability. However, DEX improved the viability and barrier damage and suppressed the apoptosis and inflammation of DSS-induced NCM460 cells. Correspondingly, the expression of inflammation-related proteins was reduced and the expression of tight junction proteins was increased in DSS-induced NCM460 cells after treatment with DEX. In addition, RhoA/ROCK signaling was activated in NCM460 cells induced by DSS, which was suppressed by DEX. The protective effects of DEX on DSS-indued NCM460 cells were reversed by U46619.
Conclusion: DEX improved viability and barrier damage while suppressed apoptosis and inflammation in DSS-indued NCM460 cells by inhibiting RhoA/ROCK signaling pathway.
References
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2. Adams SM and Bornemann PH. Ulcerative colitis. Am Family Physician. 2013;87:699–705.
3. Eisenstein M. Ulcerative colitis: Towards remission. Nature. 2018;563:S33. 10.1038/d41586-018-07276-2
4. Hou JK, El-Serag H, Thirumurthi S. Distribution and manifestations of inflammatory bowel disease in Asians, Hispanics, and African Americans: A systematic review. AmJ Gastroenterol. 2009;104:2100–9. 10.1038/ajg.2009.190
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6. Yang J, Wu Y, Xu Y, Jia J, Xi W, Deng H, et al. Dexmedetomidine resists intestinal ischemia-reperfusion injury by inhibiting TLR4/MyD88/NF-κB signaling. J Surg Res. 2021;260:350–8. 10.1016/j.jss.2020.11.041
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9. Chen CJ, Xiao P, Chen Y, Fang R. Selenium deficiency affects uterine smooth muscle contraction through regulation of the RhoA/ROCK signalling pathway in mice. Biol Trace Elem Res. 2019;192:277–86. 10.1007/s12011-019-01677-8
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16. Sun T, Gong Q, Wu Y, Shen Z, Zhang Y, Ge S, et al. Dexmedetomidine alleviates cardiomyocyte apoptosis and cardiac dysfunction may be associated with inhibition of RhoA/ROCK pathway in mice with myocardial infarction. Naunyn-Schmiedeberg’s Arch Pharmacol. 2021;394:1569–77. 10.1007/s00210-021-02082-6
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28. Wang J, Zhang C, Guo C, Li X. Chitosan ameliorates DSS-induced ulcerative colitis mice by enhancing intestinal barrier function and improving microflora. Int J Mol Sci. 2019;20:5751. 10.3390/ijms20225751
29. Al-Shboul O. The role of the RhoA/ROCK pathway in gender-dependent differences in gastric smooth muscle contraction. J Physiol Sci (JPS). 2016;66:85–92. 10.1007/s12576-015-0400-9
30. Del Re DP, Miyamoto S, Brown JH. RhoA/Rho kinase up-regulate Bax to activate a mitochondrial death pathway and induce cardiomyocyte apoptosis. J Biol Chem. 2007;282:8069–78. 10.1074/jbc.M604298200
31. Zheng X, Mai L, Wang T, Xu Y, Su Z, Chen J, et al. Brusatol-enriched brucea javanica oil ameliorated dextran sulfate sodium-induced colitis in mice: Involvement of NF-κB and RhoA/ROCK signaling pathways. BioMed Res Int. 2021;2021:5561221. 10.1155/2021/5561221
32. Wang Y, Shou Z, Fan H, Xu M, Chen Q, Tang Q, et al. Protective effects of oxymatrine against DSS-induced acute intestinal inflammation in mice via blocking the RhoA/ROCK signaling pathway. Biosci Rep. 2019;39:BSR20182297. 10.1042/BSR20182297
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