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Role of ROCK/NF-κB/AQP8 signaling in ethanol-induced intestinal epithelial barrier dysfunction.
- Source :
-
Molecular Medicine Reports . Sep2020, Vol. 22 Issue 3, p2253-2262. 10p. - Publication Year :
- 2020
-
Abstract
- The present study aimed to investigate the signaling pathways and the underlying molecular mechanisms involved in ethanol-induced intestinal epithelial barrier (IEB) dysfunction. Therefore, an in vitro experimental model of IEB was established using an ethanol-treated Caco-2 intestinal epithelial cell monolayer. The results confirmed that Rho-associated kinases (ROCKs), namely ROCK1 and ROCK2, were involved in the underlying pathway of ethanol-induced IEB dysfunction. Ethanol exposure significantly increased the expression of both ROCK isoforms and the activity of nuclear factor κB (NF-κB). Furthermore, ROCK1- and ROCK2-specific small interfering RNAs (siRNAs), and the NF-κB inhibitor ammonium pyrrolidine dithiocarbamate partially inhibited transepithelial electrical resistance in Caco-2 cells in an in vitro IEB model. In addition, ROCK1- and ROCK2-specific siRNAs inhibited the activity of NF-κB, thereby downregulating the expression of aquaporin 8 (AQP8). Taken together, the results of the present study suggested that ROCK1/ROCK2-mediated activation of NF-κB and upregulation of AQP8 expression levels may represent a novel mechanism of ethanol-induced impairment of IEB function. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 17912997
- Volume :
- 22
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Molecular Medicine Reports
- Publication Type :
- Academic Journal
- Accession number :
- 145083797
- Full Text :
- https://doi.org/10.3892/mmr.2020.11318