RRC ID 69804
著者 Shao T, Ke H, Liu R, Xu L, Han S, Zhang X, Dang Y, Jiao X, Li W, Chen ZJ, Qin Y, Zhao S.
タイトル Autophagy regulates differentiation of ovarian granulosa cells through degradation of WT1.
ジャーナル Autophagy
Abstract Ovarian granulosa cells (GCs) proliferate and differentiate along with follicular growth, and this is indispensable for oocyte development and female fertility. Although the role of macroautophagy/autophagy in ovarian function has been reported, its contribution to the regulation of GC characteristics remains elusive. The siRNA-mediated knockdown of two key autophagy-related genes ATG5 and BECN1 and the autophagy inhibitor chloroquine were used to interfere with autophagy in GCs. Inhibition of autophagy both genetically and pharmacologically resulted in decreased expression of genes associated with GC differentiation, including CYP19A1/Aromatase and FSHR, as well as in reduced estradiol synthesis. Mechanistically, when autophagy was disrupted, the transcription factor WT1 accumulated in GCs due to its insufficient degradation by the autophagic pathway, and this inhibited GC differentiation. Finally, decreased expression of several autophagy-related genes, as well as reduced LC3-II:LC3-I and elevated SQSTM1/p62 protein levels, which are indications of decreased autophagy, were detected in GCs from biochemical premature ovarian insufficiency patients. In summary, our study reveals that autophagy regulates the differentiation of ovarian GCs by degrading WT1 and that insufficient autophagy might be involved in ovarian dysfunction.
巻・号 18(8)
ページ 1864-1878
公開日 2022-8-1
DOI 10.1080/15548627.2021.2005415
PMID 35025698
PMC PMC9450966
MeSH Animals Autophagy* / genetics Chloroquine / pharmacology Estradiol / pharmacology Female Granulosa Cells* / metabolism RNA, Small Interfering / metabolism Transcription Factors / metabolism
IF 9.77
リソース情報
ヒト・動物細胞 KGN(RCB1154)