Abstract
Transforming growth factor β (TGF-β) induced differentiation of lung fibroblasts to myofibroblasts is a key event in the pathogenesis of pulmonary fibrosis. This study aimed to evaluate the effect of curcumin on TGF-β induced differentiation of lung fibroblasts to myofibroblasts and explore the underlying mechanism. Mouse lung fibroblasts were cultured and treated with TGF-β2 and curcumin or rosiglitazone. Cell vitality was examined by MTT assay. The secretion of collagen-1 was assessed by ELISA. α smooth muscle actin (α-SMA) was visualized by immunofluorescence technique. The expression of peroxisome proliferator activated receptor γ (PPAR-γ) and platelet derived growth factor R β (PDGFR-β) was detected by PCR and Western blot analysis. We found that curcumin and rosiglitazone inhibited the proliferation and TGF-β induced differentiation of mouse lung fibroblasts. In addition, curcumin and rosiglitazone inhibited collagen-1 secretion and α-SMA expression in mouse lung fibroblasts. Furthermore, curcumin and rosiglitazone upregulated PPAR-γ and downregulated PDGFR-β expression in mouse lung fibroblasts. In conclusion, our study reveals novel mechanism by which curcumin inhibits TGF-β2 driven differentiation of lung fibroblasts to myofibroblasts. Curcumin could potentially be used for effective treatment of pulmonary fibrosis.
Highlights
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown etiology that can result in respiratory failure (Meltzer and Noble, 2008; Wilson and Wynn, 2009)
Mouse lung fibroblasts were treated with curcumin or rosiglitazone at various concentrations
The results showed that curcumin and rosiglitazone inhibited the proliferation of mouse lung fibroblasts in a dose and time dependent manner (Figure 1)
Summary
Idiopathic pulmonary fibrosis (IPF) is a progressive disease of unknown etiology that can result in respiratory failure (Meltzer and Noble, 2008; Wilson and Wynn, 2009). Fibroblasts are major effector cells in the development of pulmonary fibrosis due to their ability to differentiate into myofibroblasts and produce excess ECM components, including collagen and fibronectin (Nathan et al, 2011; Olson and Swigris, 2012; Chełstowska et al, 2014). Myofibroblasts are characterized by the expression of alpha smooth muscle actin (α-SMA), calponin and ECM proteins including Type I and III collagen (Col1A1 and Col3A1), fibronectin and proteoglycan (Nathan et al, 2011). Transforming growth factor β (TGF-β) is a pleiotropic cytokine that promotes the differentiation of fibroblasts to myofibroblasts and plays a major role in fibrosis. TGF-β activates Akt signaling via p38 Mitogen Activated Protein Kinase (MAPK) and Focal Adhesion Kinase (FAK; Kulkarni et al, 2011)
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