Research Division of Food Functionality, Korea Food Research Institute, Wanju-gun, Jeollabuk-do, 55365, Republic of Korea.
Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, 55455, USA.
Exp Mol Med. 2021 Apr;53(4):548-559. doi: 10.1038/s12276-021-00611-0. Epub 2021 Apr 20.
The autophagy-lysosomal degradation system has an important role in maintaining liver homeostasis by removing unnecessary intracellular components. Impaired autophagy has been linked to nonalcoholic fatty liver disease (NAFLD), which includes hepatitis, steatosis, fibrosis, and cirrhosis. Thus, gaining an understanding of the mechanisms that regulate autophagy and how autophagy contributes to the development and progression of NAFLD has become the focus of recent studies. Autophagy regulation has been thought to be primarily regulated by cytoplasmic processes; however, recent studies have shown that microRNAs (miRNAs) and transcription factors (TFs) also act as key regulators of autophagy by targeting autophagy-related genes. In this review, we summarize the miRNAs and TFs that regulate the autophagy pathway in NAFLD. We further focus on the transcriptional and posttranscriptional regulation of autophagy and discuss the complex regulatory networks involving these regulators in autophagy. Finally, we highlight the potential of targeting miRNAs and TFs involved in the regulation of autophagy for the treatment of NAFLD.
自噬溶酶体降解系统通过清除细胞内不必要的成分,在维持肝脏内稳态方面发挥着重要作用。自噬功能受损与非酒精性脂肪性肝病(NAFLD)有关,后者包括肝炎、脂肪变性、纤维化和肝硬化。因此,了解调节自噬的机制以及自噬如何促进 NAFLD 的发生和发展已成为近期研究的重点。自噬调节被认为主要受细胞质过程调控;然而,最近的研究表明,microRNAs(miRNAs)和转录因子(TFs)也可以通过靶向自噬相关基因作为自噬的关键调节剂。在这篇综述中,我们总结了调节 NAFLD 自噬途径的 miRNAs 和 TFs。我们进一步关注自噬的转录和转录后调控,并讨论涉及这些调节剂的复杂调控网络在自噬中的作用。最后,我们强调了针对参与自噬调节的 miRNAs 和 TFs 治疗 NAFLD 的潜力。