LncPrep + 96kb inhibits ovarian fibrosis by upregulating prolyl oligopeptidase expression.

Abstract

LncPrep + 96kb is a long non‑coding RNA expressed in murine granulosa cells. The 2.2-kb fragment of lncPrep + 96kb inhibits aromatase expression and estrogen secretion in ovarian granulosa cells. In the present study, lncPrep + 96kb‑knockout (KO) mice were generated, and significant ovarian fibrosis and reduced female fertility through fertility monitoring and superovulation. The augmentation of ovarian fibrosis was observed by Sirius red staining and western blot and RT‑qPCR. Notably, lncPrep + 96kb was identified in conserved non‑coding sequences adjacent to the prolyl oligopeptidase (POP) gene. Furthermore, POP expression was shown to be reduced in lncPrep + 96kb‑KO mice, whereas overexpression of lncPrep + 96kb increased POP expression. Further studies revealed that POP regulated the expression levels of factors related to fibrosis, including matrix metalloproteinase 2 (MMP2), transforming growth factor β1 (TGF‑β1) and peroxisome proliferator activated receptor γ (PPAR‑γ). In conclusion, ovarian fibrosis was elevated in lncPrep + 96kb‑KO mice, and POP may act as a target of lncPrep + 96kb, which mediates ovarian fibrosis through the regulation of PPAR‑γ, MMP2 and TGF‑β1 expression.