Tannic acid modulates fibroblast proliferation and differentiation in response to pro-fibrotic stimuli

In response to tissue injury, fibroblasts migrate into the wound, where they undergo proliferation and differentiation. The persistence of these differentiated fibroblasts (myofibroblasts) is associated with excessive scarring in various organs. We aimed to investigate the effects of Tannic acid (TA) on fibroblast proliferation and differentiation, and found that TA inhibited fibroblast differentiation as assessed by reduced expression of α-smooth muscle actin, N-cadherin, and type-1-collagen. TA also prevented the TGF-β1-induced alteration in the expression of two classes of genes involved in the remodeling of extracellular matrix (ECM) proteins, namely matrix metalloproteinases (Mmp-2 and -9) and tissue inhibitors of metalloproteinases (Timp-1 and -3). Further, TA suppressed TGF-β1-induced cell proliferation and induced cell cycle arrest at G0/G1 phase via targeting Cyclins expression. Finally, TA exerted its inhibitory effects by decreasing the phosphorylation of Smad and ERK signaling. In sum, our results suggesting that TA may be a potential therapeutic agent for pathological fibrosis.