TGF-β1 controls porcine granulosa cell states: A miRNA-mRNA network view

Abstract

TGF-β1, an important multi-functional cytokine of the TGF-β signaling pathway, has been reported to be crucial for ovarian granulosa cell (GC) states and female fertility. However, the molecular mechanism underlying TGF-β1 regulation of GC states remains largely unknown. Here, we provide a comprehensive transcriptomic view on TGF-β1 regulation of cell states in porcine GCs. We first confirmed that TGF-β1 can control GC states (apoptosis and proliferation) in pig ovary. RNA-seq showed that 909 differentially expressed genes (DEGs), including 890 DEmRNAs and 19 DEmiRNAs, were identified in TGF-β1-treated porcine GCs. Functional annotation showed that these DEGs were mainly involved in regulating cell states. In addition, multiple hub genes were identified by constructing the protein-protein interaction network, DEmiRNA-DEmRNAs regulatory network, and gene-pathway-function co-expression networks, which were further found to be enriched in FoxO, TGF-β, Wnt, PIK3-Akt, p53 and Ras signaling pathways that play important roles in regulating cell states, cell cycle, proliferation, stress-responses and inflammation. The current research deeply reveals the effects of TGF-β1 on porcine GCs, and also identifies potential therapeutic RNA molecules for inhibiting and rescuing female infertility.

Keywords: Granulosa cells; Pig; RNA-Seq; TGF-β1; miRNA-mRNA network.