microRNA-34a调控ACSL1在胆道闭锁肝脏脂质代谢异常中的机制研究

Biliary atresia (BA) is the most common indication for pediatric liver transplantation. One of the biggest challenge in treating BA is the progressive liver fibrosis, even when the bile flow is established after a successful portoenterostomy. Our previous studies has revealed the disorder of lipometabolism in BA and ACSL1, an important enzyme in fatty acid metabolism, was down-regulated. We also found microRNA-34 was over-expressed in BA, and Bioinformatics showed ASCL1 was the target gene of microRNA-34. So we deduce that the mechanism of "microRNA34 overexpression-ASCL1 downregulation-lipometabolism disorder" exists in the liver fibrosis of BA. In this study, we would verify the mechanism, which could provide insights in intervening liver fibrosis after portoentrostomy in BA.

胆道闭锁 (Biliary Atresia, BA) 是儿童肝移植的首要病因，进行性肝纤维化和肝硬化是该病的主要特征。脂质代谢异常在肝纤维化过程中发挥重要作用，具体机制不明。本项目组前期研究发现，miRNA-34a在BA肝组织中高表达，其靶基因长链脂酰辅酶A合成酶家族成员1 (ACSL1) 表达降低，而ACSL1是肝脏脂肪酸活化的重要分子。这提示miRNA-34a可能是参与BA脂质代谢异常的调控分子。我们推测，在BA肝纤维化过程中存在”miRNA-34a高表达—ACSL1抑制—脂质代谢异常”这一机制。本课题将从人体组织、细胞和动物模型三个层次验证miRNA-34a抑制ACSL1介导脂质代谢异常的机制。本课题对揭示BA脂质代谢异常的机制具有重要意义，为干预BA肝纤维化过程提供新的思路。

胆道闭锁 (Biliary Atresia, BA) 是儿童肝移植的首要病因，进行性肝纤维化和肝硬化是该病的主要特征，具体机制不明。本项目组研究发现，miRNA-34a在BA肝组织中高表达，其靶基因长链脂酰辅酶A合成酶家族成员1 (ACSL1) 表达降低，而ACSL1在肝脏损伤过程中发挥重要作用，这提示miRNA-34a可能是参与BA肝纤维、肝硬化的调控分子；同时课题组从人体组织、细胞和动物模型三个层次展开研究，发现在BA肝纤维化过程中存在“miRNA-34a高表达—ACSL1抑制—肝纤维化、肝硬化”这一机制。本课题对揭示BA肝纤维化、肝硬化的机制具有重要意义，为干预BA肝纤维化过程提供新的思路。