miR‐181b‐induced SMAD7 downregulation controls granulosa cell apoptosis through TGF‐β signaling by interacting with the TGFBR1 promoter

SMAD7 disrupts the TGF‐β signaling pathway by influencing TGFBR1 stability and by blocking the binding of TGFBR1 to SMAD2/3. In this study, we showed that SMAD7 attenuated the TGF‐β signaling pathway in ovarian granulosa cells (GCs) by regulating TGFBR1 transcriptional activity. To function as a transcription factor, SMAD7 downregulated the mRNA levels of TGFBR1 via direct binding to the SMAD‐binding elements (SBEs) within the promoter region of pig TGFBR1. We also showed that SMAD7 enhanced porcine GC apoptosis by interrupting TGFBR1 and the TGF‐β signaling pathway. Interestingly, miR‐181b, a microRNA that is downregulated during porcine follicular atresia, was identified to be directly targeting SMAD7 at its 3′‐UTR. By inhibiting SMAD7, miR‐181b could inhibit GC apoptosis by activating the TGF‐β signaling pathway. Our findings provide new insights into the mechanisms underlying the regulation of the TGF‐β signaling pathway by SMAD7 and miR‐181b. SMAD7 acts as a pro‐apoptotic factor, potentially by antagonizing the TGF‐beta signaling pathway at the transcriptional level and interacting with miR‐181b to regulate porcine GC apoptosis.