Ursolic acid inhibits human dermal fibroblasts hyperproliferation, migration, and collagen deposition induced by TGF-β via regulating the Smad2/3 pathway.

Hypertrophic scar (HS) is a skin condition characterized by excessive fibrosis with disordered collagens from skin fibroblasts, which causes abnormal esthetic and even functional symptoms, thereby affecting millions of people. Ursolic acid (UA) is widely used in skincare and exerts anti-fibrotic effects. The present study aimed to delve into the impact of UA on HS and the mechanism. Fibroblasts (FBs) were incubated with TGF-β to investigate physiological characteristics compared with FBs isolated from normal skin (NSFBs) and hyperplastic scars (HSFBs). TGF-β-incubated FBs were subjected to treatment with UA (0-20 μM). The expressions of Vimentin, α-SMA, Collagen I, and Collagen III were examined using immunofluorescence, RT-qPCR, and western blot. Cell viability, proliferation, apoptosis, migration, and contractility were examined by CCK-8, EdU, Annexin V-FITC/PI, Transwell, and collagen gel contraction assays, respectively. The activation of Smad2/3 signaling was also determined by western blot. The binding sites for UA of TGF-βR1 (ALK5) were predicted by the Autodock tool. Compared with NSFBs, the cell proliferation, migration, and contractility of both HSFBs and TGF-β-incubated FBs were all significantly up-regulated. UA markedly impaired the TGF-β-induced increase in cell proliferation, migration, and contractility, α-SMA, collagen I, and Collagen III expression of FBs. UA significantly inhibited the phosphorylation levels of Smad2/3 in TGF-β-incubated FBs with no influence on TGF-βR1 and TGF-βR2 expressions, which might be because of the binding of UA to the catalytic domain of ALK5 protein. UA attenuated TGF-β1-induced hyperproliferation, migration, and collagen deposition in FBs via regulating the Smad2/3 pathway.