Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Department of Gastroenterology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, China.
Dig Dis Sci. 2021 Sep;66(9):3054-3061. doi: 10.1007/s10620-020-06601-y. Epub 2020 Sep 18.
Endoplasmic reticulum (ER) stress is one of the major causes to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Our previous study showed that maintains the homeostasis of ER could effectively alleviate NAFLD. In this study, we found that the loss of FAM172A increased ER stress.
The aims of this study were to explore whether FAM172A could improve NAFLD by inhibiting ER stress.
The expression levels of FAM172A and ER stress were detected by western blot. The method of immunofluorescence was used to determine FAM172A location. The interacted proteins of FAM172A were identified by immunocoprecipitation. The methods of MTS and caspase-3/7 activity were taken to confirm the effect of FAM172A on cell viability and proliferation. The expression levels of inflammation were detected by qPCR.
We confirmed that FAM172A might alleviate NAFLD through inhibiting ER stress. Loss of FAM172A increased the expressions of ATF6, peIF2α, but decreased the expression of IRE1α. Then, it was shown that FAM172A located in ER and FAM172A directly interacted with ATF6 and peIF2α and IRE1α. More importantly, the binding of FAM172A and eIF2a in tunicamycin-treated group increased significantly compared with the control group. However, the binding of FAM172A and ATF6 or IRE1α did not change. Next, we found that the lack of FAM172A could produce more apoptosis and inflammation.
Our results suggest that FAM172A improve steatosis by alleviating ER stress.
内质网（ER）应激是导致非酒精性脂肪性肝病（NAFLD）发病机制的主要原因之一。我们之前的研究表明，维持 ER 的内稳态可以有效缓解 NAFLD。在这项研究中，我们发现 FAM172A 的缺失会增加 ER 应激。
本研究旨在探讨 FAM172A 是否可以通过抑制 ER 应激来改善 NAFLD。
通过 Western blot 检测 FAM172A 和 ER 应激的表达水平。采用免疫荧光法确定 FAM172A 的位置。通过免疫沉淀鉴定 FAM172A 的相互作用蛋白。采用 MTS 和 caspase-3/7 活性测定法确定 FAM172A 对细胞活力和增殖的影响。通过 qPCR 检测炎症的表达水平。
我们证实 FAM172A 可能通过抑制 ER 应激来缓解 NAFLD。FAM172A 的缺失增加了 ATF6、peIF2α 的表达，但降低了 IRE1α 的表达。然后表明 FAM172A 位于 ER 中，并且 FAM172A 与 ATF6 和 peIF2α 以及 IRE1α 直接相互作用。更重要的是，与对照组相比，在衣霉素处理组中 FAM172A 与 eIF2a 的结合显著增加。然而，FAM172A 与 ATF6 或 IRE1α 的结合没有变化。接下来，我们发现 FAM172A 的缺乏会产生更多的细胞凋亡和炎症。
我们的结果表明，FAM172A 通过减轻 ER 应激来改善脂肪变性。
