Novel role of SF1 in alleviating thyroid-associated ophthalmopathy through the AMPK/mTOR signaling pathway

Abstract

Background/AimThyroid-associated ophthalmopathy (TAO) is a chronic autoimmune disorder characterized by an increased volume of adipose/connective tissue. This study aims to explore whether steroidogenic factor 1 (SF1) is implicated in development of TAO through the adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway. MethodsInitially, we extracted orbital preadipocytes from 10 TAO patients for culture and identification. After differentiation, cells were inoculated with plasmids with overexpressed SF1, and plasmids with siRNA against SF1, respectively. Then fat content and PGE2 secretion were measured by using ELISA. The levels of SF1, Bax, Bcl-2, Caspase3, Pref-1, PPARγ, Leptin, Adiponectin, p-AMPKαThr172, p-mTORSer2448, and p-S6KThr389 were detected by RT-qPCR and western blot analysis. Cell proliferation and apoptosis were measured by EdU and flow cytometry. ResultsTAO patients showed reduced SF1 expression in orbital preadipocytes. Overexpression of SF1 led to inhibited expression of Bcl-2, PPARγ, Leptin, Adiponectin and p-AMPKαThr172, fat content, cell proliferation and differentiation, but increased levels of Bax, Caspase3, Pref-1, p-mTORSer2448 and p-S6KThr389, PGE2 secretion and apoptosis rate. ConclusionOur result showed up-regulated SF1 may relieve TAO through suppressing cell proliferation and differentiation, but accelerating cell apoptosis by inhibiting the activation of the AMPK/mTOR signaling pathway.