miR-1306 Mediates the Feedback Regulation of the TGF-ß/SMAD Signaling Pathway in Granulosa Cells

Yang, Liu; Du, Xing; Liu, Lu; Cao, Qiuyu; Pan, Zengxiang; Li, Qifa

Recently, a few reports have revealed the mechanism of this feedback regulation, which was found to be mediated by the miR-122-5p-TGFBR2 axis in mouse skeletal muscle fibrosis [55] or by the miR-425-TGFBR2 axis in porcine GCs [9] . Among the classical TGF-β/SMAD signaling pathway, SMAD2 and SMAD3, another two SMAD proteins, were found to be feedback regulators in as early as 2001 and 1999, respectively [56, 57] . This feedback regulation has recently been demonstrated to be achieved through the miRNA-TGFBR2 axis (e.g., the miRNA-520e-TGFBR2 axis) [38] . This suggested that TGFBR2 is an important target in the feedback regulation of the SMAD protein from the classical TGF-β/SMAD signaling pathway. Another key receptor, TGFBR1, is a primary target of SMAD7 (an inhibitory SMAD protein [58] ), which further regulated the classical TGF-β/SMAD signaling pathway through negative feedback regulation. SMAD7 has been seen to regulate TGFBR1 through negative feedback in many ways [59] . In one of our recent studies, we have shown that SMAD7 directly binds to the promoter of TGFBR1 and further inhibits its transcription in porcine GCs [60] .