Diindolylmethane Attenuates TGF β Mediated Human Lung Fibroblast Proliferation

Abstract

ObjectiveIdiopathic pulmonary fibrosis (IPF) is a progressive scarring disorder characterized by the deposition of extracellular matrix causing impaired gas exchange with excessive proliferation and apoptosis‐resistant state of lung fibroblasts. Therefore, inhibitors of fibroblast proliferation offer considerable therapeutic promise. Diindolylmethane (DIM) is found in cruciferous vegetables and has been known for its anti‐cancer and anti‐proliferative properties. Surprisingly, DIM has never been studied in pulmonary fibrosis. In the current study, we tested the effect of DIM on human lung fibroblast proliferation and apoptosis.MethodsHuman lung fibroblasts were treated with TGF β, a fibroblast proliferation inducer, in the presence or absence of DIM. Proliferation and apoptosis were assessed by using commercially available kits. To further understand the mechanism of DIM, cell lysates were analyzed for gene expression analysis using RT PCR. Protein expressions were determined by western blot analysis.ResultsOur results showed that DIM suppressed TGF β induced proliferation in human lung fibroblasts but not apoptosis. In addition, DIM induced MMP1 expression and suppressed TGF β induced alpha smooth muscle actin and thrombospondin‐2 gene expression. Interestingly, DIM is not influencing ADAM‐TS2 expression (a pro‐fibrotic gene) in human lung fibroblasts.ConclusionsOur findings demonstrated that the natural dietary compound DIM attenuates TGF β mediated pro‐fibrotic effects through regulating of MMP‐1 and thrombospondin‐2 in human lung fibroblasts. These findings suggest that DIM may be a potential therapeutic target for pulmonary fibrosis.