Association of rno‐miR‐183‐96‐182 cluster with diethyinitrosamine induced liver fibrosis in Wistar rats

Abstract

Chronic liver injury due to various etiological factors including environmental carcinogens results in development of liver fibrosis. Numerous studies showed role of miRNAs in liver fibrosis. In the present study, we determined the rno-miR-183-96-182 cluster expression during hepatic fibrosis induced by diethylnitrosamine (DEN) treated Wistar rats and its association with plasma levels of circulating rno-miR-96, rno-miR-182, rno-miR-183, liver function test and lipid profile, aiming to identify their potential for histological stratification and early diagnosis of liver fibrosis. We found significant upregulation in the hepatic expression of rno-miR-183-96-182 cluster upon development of fibrosis in a DEN treated rats. Interestingly, the hepatic expression of this miRNA cluster correlates positively with the progression of fibrosis. Univariate analysis showed that hepatic expression of rno-miR-182-5p and rno-miR-183-5p and plasma activity of ALT are significant predictors of fibrosis. Multivariate logistic regression analysis revealed a panel of rno-miR-182-5p and ALT that can discriminate F2-F3 from F0-F1 (AUC = 0.87; P-value < 0.001), F4-F5-F6 from F0 to F1 (AUC = 0.981; P-value < 0.001), and F4-F5-F6 from F2 to F3 (AUC = 0.824; P-value < 0.001). A significant positive correlation of rno-miR-183-96-182 cluster members was also observed with plasma activities of ALT, AST, ALP, and levels of total cholesterol, HDLc and LDLc during fibrosis progression in DEN treated Wistar rats. Thus, it can be concluded that rno-miR-183-96-182 cluster being significantly up regulated and associated with chronic liver disease might play a role in fibrosis maintenance and progression. A panel of rno-miR-182-5p and ALT being significant predictors of fibrosis might improve histological stratification of fibrosis staging.

Pulmonary Silicosis Alters MicroRNA Expression in Rat Lung and miR-411-3p Exerts Anti-fibrotic Effects by Inhibiting MRTF-A/SRF Signaling

“…20 Moreover, miR-146b-5p and miR-146b-5p have been shown to be upregulated in various models of kidney injury, 21 while miR-183-5p has been shown to be a significant predictor of experimentally induced liver fibrosis. 22 Although the focus of our study was pulmonary silicosis, we believe that our findings may have broader implications for the pulmonary fibrosis field. This is because several of the miRNAs that were altered in the silicotic lung were also altered in cultured fibroblasts exposed to TGF-b1.…”

let-7a suppresses liver fibrosis via TGFβ/SMAD signaling transduction pathway

“…The most common pathological outcome and the most severe complication of chronic liver diseases are liver fibrosis which are global health and economic burdens (2). Liver fibrosis characteristically show over-accumulation of extracellular matrix (ECM), mainly type I fibrillar collagen (Collagen I) in response to chronic liver damage (3). Various etiological factors and stimuli can result in development of liver fibrosis, including viral hepatitis (hepatitis C and B), environmental carcinogens, excessive ethanol consumption, activated hepatic stellate cells (HSCs) and non-alcoholic steatohepatitis (NASH) (4,5).…”

miR-183-5p Inhibits Occurrence and Progression of Acute Myeloid Leukemia via Targeting Erbin

“…Some phenotypes also show tumor suppressor activity, suggesting that its tumorigenicity may be dependent on the environment and cell type. 18 Moreover, ectopic overexpression of miR-183 in medulloblastoma cells cultured in Ptch1 +/− /PtenFloxp −/+ transgenic mice exhibits enhanced proliferative capacity. 19 In addition, miR-183 is highly expressed in colorectal cancer and hepatocellular carcinoma, and its tumorigenicity is mainly achieved by suppressing tumor suppressor mRNA.…”