Abstract
To explore the role of the miRNA-1297/phospholipase Cβ1 (PLCβ1) axis in intestinal barrier injury. Abnormally expressed miR-1297 and its target gene PLCβ1 as well as their transcriptome sequencing were confirmed by bioinformatics analysis. Next, the intestinal barrier injury was induced by lipopolysaccharide (LPS) in the CCCHIE-2 cells. Subsequently, the impacts of miR-1297 and PLCβ1 on the transcriptome were estimated. QRT-PCR and Western blotting were conducted to detect the relative mRNA and protein expressions, respectively. The cell viability and permeability were analyzed by MTT assay and fluorescent yellow detection. miR-1297 was significantly upregulated in patients with human immunodeficiency virus/acquired immunodeficiency syndrome and targeted PLCβ1. Moreover, overexpressed PLCβ1 was mainly enriched in the transforming growth factor-beta signaling pathway, while the knockdown of miR-1297 was focused on the arginine biosynthesis pathway. The overexpression of miR-1297 could reduce the PLCβ1 expression and inhibit the viability of CCCHIE-2 cells injured by LPS, while the effect of the downregulation of miR-1297 was on the opposite. Western blotting and cell fluorescence localization experiments revealed that the inhibition of miR-1297 increased the expressions of PLCβ1 and ZO-1. In addition, the upregulation of miR-1297 strengthened the permeability in cells injured by LPS, as did the knockdown of PLCβ1. miR-1297 could restrain the repair of intestinal barrier injury via negatively regulating PLCβ1 and its tight junction downstream protein ZO-1 in CCC-HIE-2 cells injured by LPS, which indicated that PLCβ1 and miR-1297 might be important targets for the repair of intestinal barrier injury.
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This research was supported by the Basic Research Plan of Yunnan Province (Joint Project of Kunming Medical College) (No. 2019FE001 (-221)).
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JG conceived and supervised the study; YB and JG designed the experiments; YB and HG performed the experiments; BY provided new tools and reagents; FC and ZZ collected and analyzed the data; YB wrote the manuscript; JG made manuscript revisions.
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Bao, Y., Guo, H., Yang, B. et al. MicroRNA-1297 participates in the repair of intestinal barrier injury in patients with HIV/AIDS via negative regulation of PLCβ1. Mol Cell Biochem 477, 2133–2147 (2022). https://doi.org/10.1007/s11010-022-04426-z
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DOI: https://doi.org/10.1007/s11010-022-04426-z