Silencing of microRNA-375 affects immune function in mice with liver failure by upregulating astrocyte elevated gene-1 through reducing apoptosis of Kupffer cells.

Autor: Ke QH; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., Chen HY; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., He ZL; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., Lv Z; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., Xu XF; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., Qian YG; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China., Zheng SS; Division of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang University, Hangzhou, China.
Jazyk: angličtina
Zdroj: Journal of cellular biochemistry [J Cell Biochem] 2019 Jan; Vol. 120 (1), pp. 253-263. Date of Electronic Publication: 2018 Sep 11.
DOI: 10.1002/jcb.27338
Abstrakt: This study aims to investigate how microRNA-375 (miR-375) improves immune function by regulating liver macrophages (Kupffer cells) in mice with liver failure. Forty mice were divided into ConA-1h, ConA-3h, ConA-6h, and control groups, with 10 mice in each group. Mice models of liver failure were established by injecting concanavalin A (ConA) solution via the tail veins of mice, and then primary Kupffer cells were isolated and cultured. Reverse transcription quantitative polymerase chain reaction, Western blot analysis, and enzyme-linked immunosorbent assay were conducted to examine the expressions of miR-375, astrocyte elevated gene-1 (AEG-1), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and IL-1β in Kupffer cells of mice with liver failure as well as after silencing of miR-375. Flow cytometry was used to determine cell apoptosis. During the liver failure process, miR-375, IL-6, TNF-α, and IL-1β expressions were increased over time, while AEG-1 expression decreased over time in the control, ConA-1h, ConA-3h, and ConA-6h groups. Opposite alternations were observed after silencing of miR-375. Dual-luciferase reporter gene assay showed that AEG-1 was a target gene of miR-375. Flow cytometry determination showed that the ratio of apoptotic Kupffer cells decreased after silencing of miR-375. Overexpression of AEG-1 could rescue the suppression of IL-6, TNF-α, and IL-1β expressions in Kupffer cells after the short-term induction of ConA and further inhibit cell apoptosis. Our study provides evidence that miR-375 could regulate Kupffer cells to improve immune function in mice with liver failure.
(© 2018 Wiley Periodicals, Inc.)
Databáze: MEDLINE
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