MicroRNA-21 via Dysregulation of WW Domain-Containing Protein 1 Regulate Atrial Fibrosis in Atrial Fibrillation

Background microRNAs (miRs) have been reported to regulate cell biological functions. To explore the underlying mechanism of miR-21 involvement in patients with atrial fibrosis and atrial fibrillation (AF). Methods In total, 49 patients (24 AF, sinus rhythm 25) aged 33-68 years old, including heart valve replacement surgery and cardiac catheterisation. The pathological changes and collagen depositions was analysed by Masson's Trichrome Staining. miR-21, TGF-beta 1, Smad2, p-Smad2, WWP-1, collagen I and collagen III expression were analysed by Western blotting, qRT-PCR, miR one step qRT-PCR, respectively. Treatment human cardiac fibroblasts with TGF-beta 1, qRT-PCR and Western blotting to find changes in miR-21, Smad2 and WWP-1 levels. Transfected human cardiac fibroblasts with miR-21 mimic and miR-21 inhibitor. Finally, cell proliferation ability was assessed by the MTT assay and flow cytometry. Results Compared to sinus rhythm (SR) group, the collagen volume fraction was significantly increased in AF patients. The levels of the TGF-beta 1, collagen I and collagen III were significantly elevated in AF group. In AF patients, the expression of miR-21 was increased, while the expression of WWP-1 was decreased. Transfected cardiac fibroblasts with miR-21 mimic increased miR-21 expression and decreased WWP-1 expression, whereas miR-21 inhibitor causes the opposite effects. Additionally, we demonstrated that knockdown miR-21 targeted up-regulation of WWP-1 may suppress cardiac fibroblasts proliferation. Conclusion These indicated that miR-21 inhibits cardiac fibroblasts proliferation by inactivating the TGF-beta 1/Smad2 signaling pathway via up-regulation of WWP-1.