Abstract
Acute pancreatitis (AP) causes intestinal barrier damage, resulting in systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS), which are important factors affecting AP severity and mortality. Here, we studied the mechanism of miR-122 in regulating intestinal barrier function in AP. AP rat model was constructed via intraperitoneal injection of ketamine, and primary intestinal epithelial cells were isolated from rats for in vitro studies. HE staining was used to assess pathological alterations of pancreas and intestines tissues. Inflammatory factors were detected by ELISA assay. qRT-PCR and WB were used to detect the expressions of miR-122 and occluding, respectively. Then dual-luciferase reporter assay, intestinal permeability test, and cell permeability were performed in vivo and in vitro to probe the molecular mechanism of miR-122 in regulating intestinal barrier function in AP. The expression of miR-122 was upregulated in AP rats, while the expression of occludin was downregulated, and the intestinal permeability was increased in AP rats and primary intestinal epithelial cells isolated from rats. Inhibition of miR-122 regulated intestinal barrier function through mediating occludin expression. miR-122 regulated intestinal barrier function to affect AP through mediating occludin expression in vivo. These results provided evidence that miR-122 overexpression impaired intestinal barrier function via regulation of occludin expression, thus promoting AP progression.
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All data generated or analyzed during this study are included in this published article.
Abbreviations
- AP:
-
Acute pancreatitis
- SIRS:
-
Systemic inflammatory response syndrome
- MODS:
-
Multiple organ dysfunction syndromec
- miR:
-
MicroRNA
- SAP:
-
Severe acute pancreatitis
- UTR:
-
Untranslated region
- IL-1β:
-
Interleukin-1β
- TNFα:
-
Tumor necrosis factorα
- qRT-PCR:
-
Quantitative real-time polymerase chain reaction
- GAPDH:
-
Glyceraldehyde 3-phosphate dehydrogenase
- SDS-PAGE:
-
Sodium dodecyl sulfate–polyacrylamide gel electrophoresis
- ELISA:
-
Enzyme-linked immunosorbent assay
- SEM:
-
Standard error of the mean
- ANOVA:
-
Analysis of variance
- WB:
-
Western blot
- HE:
-
Hematoxylin–eosin
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Thanks to the members of our laboratory for their contributions.
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This work was supported by grants from Kunshan Social Development of Science and Technology Program (No. KS1549; No. KS1648) and Suzhou Clinical Medicine Expert Team Project (No. SZYJTD201722).
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Yang, W., Xu, HW., Lu, XR. et al. Overexpression of miR-122 Impairs Intestinal Barrier Function and Aggravates Acute Pancreatitis by Downregulating Occludin Expression. Biochem Genet 60, 382–394 (2022). https://doi.org/10.1007/s10528-021-10106-2
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DOI: https://doi.org/10.1007/s10528-021-10106-2