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Effect of miR‐182 on hepatic fibrosis induced by Schistosomiasis japonica by targeting FOXO1 through PI3K / AKT signaling pathway
Author(s) -
Huang Yu,
Fan Xiangxue,
Tao Ran,
Song Qiqin,
Wang Likui,
Zhang Hongyue,
Kong Hongyan,
Huang Jiaquan
Publication year - 2018
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.26469
Subject(s) - foxo1 , pi3k/akt/mtor pathway , protein kinase b , western blot , hepatic fibrosis , biology , viability assay , cell growth , cancer research , apoptosis , microbiology and biotechnology , fibrosis , transfection , ctgf , microrna , signal transduction , cell culture , pathology , medicine , growth factor , receptor , biochemistry , gene , genetics
The study aimed to investigate the impact of miR‐182 and FOXO1 on S. japonica ‐induced hepatic fibrosis. Microarray analysis was performed to screen out differential expressed miRNAs and mRNAs. Rat hepatic fibrosis model and human hepatocellular cell line LX‐2 were used to study the effect of miR‐182 and FOXO1 . qRT‐PCR and Western blot were used to detect the expression of miR‐182, FOXO1 or other fibrosis markers. The targeting relationship between FOXO1 and miR‐182 was verified by luciferase reporter assay. Immunohistochemistry or immunofluorescence staining was conducted to detect FOXO1 or α‐SMA in rat hepatic tissues. Cell viability and apoptosis were detected by MTT assay and flow cytometry. The expression of PI3K / AKT pathway‐related proteins was detected by Western blot. miR‐182 was highly expressed in liver fibrosis samples, and FOXO1 expression was negatively correlated with miR‐182 expression. After transfection of miR‐182, FOXO1 expression was down‐regulated, with the results of LX‐2 cells proliferation inhibition and apoptosis induction, as well as the aggravation of rat hepatic fibrosis. The expression of p‐AKT/AKT and p‐S6/S6 was increased, meaning that the PI3K / AKT signal pathway was activated. The results were reversed when treated with Wortmannin ( PI3K inhibitor). After transfection of miR‐182 inhibitor, FOXO1 expression was up‐regulated, LX‐2 cell proliferation was inhibited, and apoptosis rate was increased. High‐expressed miR‐182 and low‐expressed FOXO1 promoted proliferation and inhibiting apoptosis on liver fibrosis cells, stimulating the development of S. japonica ‐induced hepatic fibrosis through feeding back to PI3K/AKT signaling pathway.