Oleanolic acid regulates the proliferation and extracellular matrix of keloid fibroblasts by mediating the TGF-β1/SMAD signaling pathway.

Abstract

Keloid (KD) is a unique pathological fibroproliferative disease that seriously affects the appearance of patients. This study investigated the effect of oleanolic acid (OA) on the proliferation of keloid fibroblasts (KFs) and the expression of extracellular matrix (ECM)-related proteins. The proliferation of KFs was evaluated using an MTT assay. The effects of OA on intra- and extracellular levels of fibronectin (FN), procollagen I, matrix metalloproteinase-1 (MMP-1), and α-smooth muscle actin (α-SMA) were evaluated using Western blotting. To simulate the KD microenvironment, TGF-β1 was added to the serum-free culture medium, and KFs were incubated with TGF-β1 and OA for 24 h. The intra- and extracellular levels of the ECM-related proteins and the effect of OA on TGF-β1-induced phosphorylation of the SMAD2 and SMAD3 proteins were evaluated using Western blotting. OA inhibited the proliferation of KFs in a concentration- and time-dependent manner. Furthermore, OA treatment of KFs reduced the intra- and extracellular levels of FN, procollagen I, and α-SMA and increased those of MMP-1. OA also reduced TGF-β1-induced increases in the intra- and extracellular levels of FN, procollagen I, and α-SMA and increased the levels of the MMP-1 protein. Additionally, OA significantly reduced TGF-β1-induced phosphorylation of SMAD2 and SMAD3 in KFs. OA inhibited KF proliferation and reduced ECM deposition through the TGF-β1/SMAD pathway, which suggests that OA may be an effective drug for the prevention and treatment of KD.