Rho/Rock cross‑talks with transforming growth factor‑β/Smad pathway participates in lung fibroblast‑myofibroblast differentiation
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- Published online on: July 31, 2014 https://doi.org/10.3892/br.2014.323
- Pages: 787-792
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Abstract
The differentiation of fibroblasts, which are promoted by transforming growth factor‑β (TGF‑β)/Smad, is involved in the process of pulmonary fibrosis. The Rho/Rho‑associated coiled‑coil‑forming protein kinase (Rock) pathway may regulate the fibroblast differentiation and myofibroblast expression of α‑smooth muscle actin (α‑SMA), however, the mechanism is not clear. The aim of the present study was to evaluate the role of Rho/Rock and TGF‑β/Smad in TGF‑β1‑induced lung fibroblasts differentiation. Human embryonic lung fibroblasts were stimulated by TGF‑β1, Y‑27632 (inhibitor of Rho/Rock signaling) and staurosporine (inhibitor of TGF‑β/Smad signaling). The α‑SMA expression, cell cycle progression, content of the extracellular matrix (ECM) in cell culture supernatants and the expression of RhoA, RhoC, Rock1 and Smad2 were detected. The results demonstrated that α‑SMA‑positive cells significantly increased following TGF‑β1 stimulation. Rho/Rock and TGF‑β/Smad inhibitors suppressed TGF‑β1‑induced lung fibroblast differentiation. The inhibitors increased G0/G1 and decreased S and G2/M percentages. The concentrations of the ECM proteins in the supernatant were significantly increased by TGF‑β1 stimulation, whereas they were decreased by inhibitor stimulation. RhoA, RhoC, Rock1, Smad2 and tissue inhibitor of metalloproteinase‑1 were upregulated by TGF‑β1 stimulation. The Rho/Rock inhibitor downregulated Smad2 expression and the TGF‑β/Smad inhibitor downregulated RhoA, RhoC and Rock1 expression. Therefore, the Rho/Rock pathway and Smad signaling were involved in the process of lung fibroblasts transformation, induced by TGF‑β1, to myofibroblasts. The two pathways may undergo cross‑talk in the lung fibroblasts differentiation in vitro.
