Cholangiocyte-derived exosomal long noncoding RNA PICALM-AU1 promotes pulmonary endothelial cell endothelial-mesenchymal transition in hepatopulmonary syndrome

作者全名："Yang, Congwen; Yang, Yihui; Chen, Yang; Huang, Jian; Li, Dan; Tang, Xi; Ning, Jiaolin; Gu, Jianteng; Yi, Bin; Lu, Kaizhi"

作者地址："[Yang, Congwen; Chen, Yang; Huang, Jian; Li, Dan; Tang, Xi; Ning, Jiaolin; Gu, Jianteng; Yi, Bin; Lu, Kaizhi] Third Mil Med Univ, Southwest Hosp, Dept Anesthesia, Chongqing 400038, Peoples R China; [Yang, Congwen] Chongqing Med Univ, Chongqing Key Lab Tradit Chinese Med Prevent & Cur, Chongqing 400016, Peoples R China; [Yang, Yihui] Zunyi Med Univ, Affiliated Hosp 3, Dept Anesthesia, Zunyi 563000, Guizhou, Peoples R China"

通信作者："Yi, B; Lu, KZ (通讯作者)，Third Mil Med Univ, Southwest Hosp, Dept Anesthesia, Chongqing 400038, Peoples R China."

来源：HELIYON

ESI学科分类：　

WOS号：WOS:001175390700001

JCR分区：Q1

影响因子：3.4

年份：2024

卷号：10

期号：3

开始页：　

结束页：　

文献类型：Article

关键词：Long noncoding RNA (lncRNA); PICALM-AU1; Endothelial-mesenchymal transition (EndMT); Hepatopulmonary syndrome

摘要："Hepatopulmonary syndrome (HPS) is a severe lung injury caused by chronic liver disease, with limited understanding of the disease pathology. Exosomes are important mediators of intercellular communication that modulates various cellular functions by transferring a variety of intracellular components to target cells. Our recent studies have indicated that a new long noncoding RNA (lncRNA), PICALM-AU1, is mainly expressed in cholangiocytes, and is dramatically induced in the liver during HPS. However, the mechanism by which cholangiocyte-derived PICALM-AU1 regulates Endothelial-mesenchymal transition (EndMT) in HPS remains unclear. Here, we observed that PICALM-AU1 was synthesized in the cholangiocytes of the liver and then, secreted as exosomes into the serum; serum exosomal PICALM-AU1 levels were positively correlated with the severity of HPS in a rat model and in human patients. PICALM-AU1 carrying serum exosomes induced the EndMT of pulmonary microvascular endothelial cells (PMVECs) and promoted lung injury in vivo and in vitro. Furthermore, PICALM-AU1 acted as a molecular sponge for microRNA 144-3p (miR144-3p), resulting in the up-regulation of Zinc Finger E-Box Binding Homeobox 1 (ZEB1), a known target of EndMT and enhancement of EndMT, proliferation and migration of PMVECs. Taken together, our findings indicate that the cholangiocyte-derived exosomal lncRNA PICALM-AU1 plays a critical role in the EndMT in HPS lungs. Thus, it represents a potential therapeutic target for the treatment of HPS."

基金机构："National Natural Science Foundation of China [81800060, 81671961, 81700046]; Natural Science Foundation of Chongqing, China [cstc2020jcyj-msxmX0361]; Science and Technology Project Affiliated to the Edu- cation Department of Chongqing Municipality [KJZD-K202215104]"

基金资助正文："This project was supported by the National Natural Science Foundation of China (81800060, 81671961, 81700046) and Natural Science Foundation of Chongqing, China (cstc2020jcyj-msxmX0361) and The Science and Technology Project Affiliated to the Edu- cation Department of Chongqing Municipality (KJZD-K202215104) ."