Chen Dahua, Dong Xiaoqi, Chen Dawei, Lin Jieqiong, Lu Ting, Shen Jianwei, Ye Hua
Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, 315040, Zhejiang Province, PR China.
Department of Pulmonary and Critical Care Medicine, Ningbo Medical Center Lihuili Hospital (Lihuili Hospital Affiliated to Ningbo University), Ningbo, 315040, Zhejiang Province, PR China.
Biochem Biophys Res Commun. 2023 Nov 12;681:13-19. doi: 10.1016/j.bbrc.2023.09.038. Epub 2023 Sep 17.
Nonalcoholic fatty liver disease (NAFLD) is a significant etiological factor in liver-related diseases, which can lead to severe consequences such as steatohepatitis, cirrhosis and death. Cdh1 is considered as a crucial protein involved in cell cycle regulation. The purpose of this study is to explore the biological role of Cdh1 in NAFLD.
NAFLD cell model was established, and L02 cells and AML12 cells were infected by shRNA lentivirus with Cdh1 knockdown in vitro, and the effect of Cdh1 deletion on cell lipid deposition was evaluated. The effects of Cdh1 deletion on Akt phosphorylation and PPAR/PGC-1α signaling pathway in L02 cells were examined. In addition, the NAFLD mouse model was constructed, and the conditional knockout mice of Cdh1 were selected to verify the results.
In vitro experiments showed that the Cdh1 deletion enhanced cell lipid deposition. In vivo experiments showed that conditional knockdown of Cdh1 aggravated fatty degeneration and damage of liver in mice. Cdh1 deletion promotes Akt phosphorylation and inhibits PPAR/PGC-1α signaling pathway in L02 cells. Conditional knockout of Cdh1 down-regulates PPAR/PGC-1α signaling pathway in NAFLD mouse model.
The deletion of Cdh1 may promote Akt phosphorylation by up-regulating Skp2 and inhibit the PPAR/PGC-1α signaling pathway. Cdh1 serves a protective function in the occurrence and progression of NAFLD.
非酒精性脂肪性肝病（NAFLD）是肝脏相关疾病的一个重要病因，可导致诸如脂肪性肝炎、肝硬化和死亡等严重后果。Cdh1被认为是参与细胞周期调控的关键蛋白。本研究的目的是探讨Cdh1在NAFLD中的生物学作用。
建立NAFLD细胞模型，在体外通过shRNA慢病毒感染L02细胞和AML12细胞以敲低Cdh1，评估Cdh1缺失对细胞脂质沉积的影响。检测Cdh1缺失对L02细胞中Akt磷酸化和PPAR/PGC-1α信号通路的影响。此外，构建NAFLD小鼠模型，选择Cdh1条件性敲除小鼠以验证结果。
体外实验表明，Cdh1缺失增强了细胞脂质沉积。体内实验表明，Cdh1的条件性敲低加重了小鼠肝脏的脂肪变性和损伤。Cdh1缺失促进L02细胞中Akt磷酸化并抑制PPAR/PGC-1α信号通路。在NAFLD小鼠模型中，Cdh1的条件性敲除下调了PPAR/PGC-1α信号通路。
Cdh1的缺失可能通过上调Skp2促进Akt磷酸化并抑制PPAR/PGC-1α信号通路。Cdh1在NAFLD的发生和发展中起保护作用。
