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

The transforming growth factor beta (TGF-β)/SMA-and MAD-related protein (SMAD) signaling pathway plays a significant role in regulating numerous processes in the cell, including cellular proliferation [1] , differentiation [2] , and the cell cycle [3] , as well as apoptosis [4] , by introducing extracellular signal transduces into the cell nucleus. The classic TGF-β/SMAD signaling pathway consists of a ligand (TGF-β1) and two transmembrane serine-threonine kinase receptors, namely TGF-β receptor I (TGFBR1 or ALK5) and TGF-β receptor II (TGFBR2), as well as SMADs (SMAD2/3/4). Activation of the signal depends on the interaction between the ligand and TGFBR2 leading to the dimerization of TGFBR2 and TGFBR1. During this process, TGFBR1 is phosphorylated and activated by the kinase activity of TGFBR2. Activated TGFBR1 phosphorylates downstream molecules SMAD2 and SMAD3, subsequently leading to the formation of a trimeric complex with SMAD4. Finally, this complex translocates into the nucleus and modulates downstream gene transcription in response to extracellular signals [5] . Therefore, as a core transmembrane receptor, TGFBR2 plays a significant role in the TGF-β signal transduction. For example, odontoblast-specific TGFBR2 conditional knockout in mice results in the loss of responsiveness to TGF-β along with inactivation of the TGF-β/SMAD pathway, causing impaired matrix formation and pulpal obliteration in odontoblasts [6] .