Figure 9. Schematic illustration of the mechanism linking miR-181b and Sema3A in a fundamental TGF-β-induced EndMT process and atrial subendocardial fibrosis.

(A) A mechanism of fundamental TGF-β–induced EndMT and atrial subendocardial fibrosis was identified. (B) TGF-β activates p-SMAD3, which binds to SMAD4 and forms the SMAD complex. This complex translocates to the nucleus and promotes miR-181b transcription. Mature miR-181b targets the 3′-UTR of Sema3A mRNA for degradation. Insufficient expression of Sema3A protein, which is needed to increase LIMK/p-cofilin signaling, leads to actin remodeling, lamellipodium formation, increased SMA stabilization, and the EndMT process, thus participating in the atrial fibrosis.