miR-505-5p alleviates acute rejection of liver transplantation by inhibiting Myd88 and inducing M2 polarization of Kupffer cells

作者全名："Chai, Hao; Lei, Zilun; Liu, Yanyao; Gong, Junhua; Cao, Zhenrui; Huang, Zuotian; Yang, Hang; Wu, Zhongjun"

作者地址："[Chai, Hao; Lei, Zilun; Liu, Yanyao; Gong, Junhua; Cao, Zhenrui; Huang, Zuotian; Yang, Hang; Wu, Zhongjun] Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400042, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，Chongqing Med Univ, Dept Hepatobiliary Surg, Affiliated Hosp 1, Chongqing 400042, Peoples R China."

来源：ACTA BIOCHIMICA ET BIOPHYSICA SINICA

ESI学科分类：BIOLOGY & BIOCHEMISTRY

WOS号：WOS:000860491100012

JCR分区：Q2

影响因子：3.7

年份：2022

卷号：54

期号：8

开始页：1148

结束页：1158

文献类型：Article

关键词：immune tolerance; liver transplantation; macrophages; miR-505-5p; Myd88

摘要："The occurrence of acute rejection after liver transplantation seriously impairs the prognosis of patients. miRNA is involved in many physiological and pathological processes of the body, but the mechanism of miRNA action in liver transplantation is not completely clear. In this study, we discuss the role of miR-505-5p in acute rejection after liver transplantation and its putative regulating mechanism. We construct an allogeneic rat liver transplantation model, observe the morphological and pathological changes in liver tissue, detect the expression levels of Myd88, miR-5055p, IL-10 and TNF-alpha, and confirm that Myd88 is one of the direct targets of miR-505. The effects of miR-505-5p on the Myd88/TRAF6/NF-kappa B and MAPK pathways are detected both in vitro and in vivo, and the standard markers of Kupffer cell M1/M2 polarization are also detected. The results of qRT-PCR experiments show that miR-505-5p has a downward trend in rats with acute rejection. Western blot analysis reveals that over-expression of miR-505-5p induces the reduction of NF-kappa B and MAPK pathways both in vitro and in vivo. The role of miR-505-5p in alleviating acute rejection after transplantation may be accomplished by inducing M2-type polarization of Kupffer cells. In conclusion, we find that miR-505-5p alleviates acute rejection of liver transplantation by inducing M2 polarization of macrophages via the Myd88/TRAF6 axis, which suggests a potential strategy based on miRNAs in the follow-up treatment of liver transplantation."

基金机构："National Natural Science Foundation of China [82170666, 81873592]"

基金资助正文：This work was supported by the grants from the National Natural Science Foundation of China (No. 82170666 and No. 81873592).