Curcumin Inhibits Transforming Growth Factor β Induced Differentiation of Mouse Lung Fibroblasts to Myofibroblasts

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.

Curcumin inhibits the TGF-β1-dependent differentiation of lung fibroblasts via PPARγ-driven upregulation of cathepsins B and L

“…Following curcumin treatment, the levels of both soluble and insoluble collagen were similar to their observed constitutive level for undifferentiated fibroblasts, attesting that curcumin down-regulated both TGF-β1 and collagen I expression and thus could impair or delay myofibrogenesis. In agreement with these results, it has been shown that curcumin inhibits both myofibrogenesis and collagen secretion in mice following bleomycin-induced lung injury 39,45 . Likewise, curcumin attenuated type I collagen production in an experimental pulmonary fibrosis in rats and showed beneficial antifibrotic effects in a rodent model of obstructive nephropathy 46,47 .…”

Soluble Dipeptidyl Peptidase-4 Induces Fibroblast Activation Through Proteinase-Activated Receptor-2

“…The SMAD2/3 intracellular pathway was heavily implicated in TGF-β-induced fibrosis and is known as the canonical pathway ( He and Dai, 2015 ). Targeting the SMAD signaling pathway is a novel therapeutic approach to treating tissue fibrosis ( Wojcik et al., 2013 ; He and Dai, 2015 ; Liu et al., 2016 ; Tee et al., 2018 ; Zhang et al., 2018 ). In addition to activating the SMAD-dependent pathway, TGF-β can signal in a noncanonical manner, as exemplified in MAPK and NF-κB signaling, which together induce a complete TGF-β response ( Wu et al., 2019 ).…”

Regulation of Transforming Growth Factor‐β/Smad‐mediated Epithelial–Mesenchymal Transition by Celastrol Provides Protection against Bleomycin‐induced Pulmonary Fibrosis

“…The inflammatory cells produced in response to TGF‐β, further induces epithelial cell injury and these cascades of events result in extracellular matrix (ECM) degradation and tissue scar formation . Several recent studies suggest that targeting the TGF signalling reduces the extent of PF in experimental models .…”