"miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages"

作者全名："Cao, Zhen-Rui; Zheng, Wei-Xiong; Jiang, Yu-Xin; Chai, Hao; Gong, Jun-Hua; Zhao, Min-Jie; Yan, Ping; Liu, Yan-Yao; Liu, Xiao-Ya; Huang, Zuo-Tian; Yang, Hang; Peng, Da-Di; Zong, Ke-Zhen; Wu, Zhong-Jun"

作者地址："[Cao, Zhen-Rui; Zheng, Wei-Xiong; Chai, Hao; Yan, Ping; Liu, Yan-Yao; Huang, Zuo-Tian; Yang, Hang; Peng, Da-Di; Zong, Ke-Zhen; Wu, Zhong-Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Jiang, Yu-Xin] Chongqing Med Univ, Affiliated Hosp 1, Dept Dermatol, Chongqing, Peoples R China; [Gong, Jun-Hua; Zhao, Min-Jie] Chongqing Med Univ, Affiliated Hosp 2, Dept Hepatobiliary Surg, Chongqing, Peoples R China; [Liu, Xiao-Ya] Chongqing Med Univ, Affiliated Hosp 1, Dept Oncol, Chongqing, Peoples R China; [Wu, Zhong-Jun] Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China"

通信作者："Wu, ZJ (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Hepatobiliary Surg, 1 Youyi Rd, Chongqing 400016, Peoples R China."

来源：AMERICAN JOURNAL OF TRANSPLANTATION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:000958458600001

JCR分区：Q1

影响因子：8.9

年份：2023

卷号：23

期号：3

开始页：336

结束页：352

文献类型：Article

关键词：basic (laboratory) research; science; liver transplantation; hepatology; immunobiology; animal models; innate immunity; macrophage; monocyte biology; activation; rejection; acute; acute rejection; miR-449a; PLOD1; NF-?B; in flammation

摘要："Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-?B) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-?B pathway. Overall, miR-449a inhibited the NF-?B pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR."

基金机构："National Natural Science Foundation of China [82170666, 81873592]; Chongqing Research Program of Technological Innovation and Application Demonstration [cstc2021jscx-gksbX0060]"

基金资助正文：Funding This study was funded by the National Natural Science Foundation of China under grants No. 82170666 and 81873592 and Chongqing Research Program of Technological Innovation and Application Demonstration under grant cstc2021jscx-gksbX0060.