TGF-β1 Regulates Smooth Muscle Cells Differentiation from Adipose-Derived Stem Cells via the Wnt/β-Catenin Pathway

Abstract Background: Pelvic floor dysfunction (PFD) is a spectrum of disorders including stress urinary incontinence and pelvic organ prolapse. Transforming growth factor-β1 (TGF-β1) can induce mesenchymal stem cells (MSCs) to differentiate into smooth muscle cells (SMCs). SMCs derived from adipose-derived stem cells (ADSCs) can be used to repair damaged pelvic floor smooth muscle tissues, which is of great interest for clinical applications using stem cell therapy for PFD. The Wnt/β-catenin pathway acts as a decisive factor in the fate of stem cells.Methods and Results: In this study, we used medium containing TGF-β1, TGF-β1 inhibitor LY2109761, or Wnt/β-catenin inhibitor KYA1797K, to induce ADCSs to differentiate into SMCs in vitro to explore the influence of TGF-β1 on the myogenic differentiation of ADCSs via the Wnt/β-catenin pathway. Results: 1) TGF-β1 induces ADSC-derived SMCs to hyper-express the SMC markers including SMA-α, Desmin, Calponin, and SMMHC ; 2) TGF-β1 activates the Wnt/β-catenin signaling pathway in ADSCs. After blocking TGF-β1, the Wnt/β-catenin pathway and myogenic differentiation in cells were inhibited; 3) the Wnt/β-catenin pathway is involved in the differentiation of ADSCs into SMCs. After differentiation induction, the synchronized changes in the activation of Wnt/β-catenin signaling and the expression of SMC-specific proteins showed a trend of simultaneous changes, and after the inhibition of the Wnt pathway, the adult muscle differentiation was significantly inhibited.Conclusions: We established a simpler and more efficient method for inducing ADSCs to differentiate into SMCs using TGF-β1 and demonstrated that the Wnt/β-catenin signaling pathway is activated during this process.