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. 2016 Nov 8:7:419.
doi: 10.3389/fphar.2016.00419. eCollection 2016.

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

Daishun Liu  1 , Ling Gong  1 , Honglan Zhu  1 , Shenglan Pu  1 , Yang Wu  1 , Wei Zhang  1 , Guichuan Huang  1
Affiliations

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

Daishun Liu et al. Front Pharmacol. .

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.

Keywords: curcumin; peroxisome proliferator activated receptor γ; platelet derived growth factor receptor β; pulmonary fibrosis; transforming growth factor β2.

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Figures

FIGURE 1
FIGURE 1
Curcumin inhibits transforming growth factor β (TGF-β2) induced proliferation of mouse lung fibroblasts. Mouse lung fibroblasts were treated with various concentrations of curcumin and rosiglitazone in the absence or presence of TGF-β2. Cell proliferation was assessed at 0, 24, 48, and 72 h. Data were presented as mean ± SEM. Cur, curcumin; Rosi, rosiglitazone.
FIGURE 2
FIGURE 2
Curcumin inhibits TGF-β2 induced morphological changes of mouse lung fibroblasts. Mouse lung fibroblasts were treated with vehicle, TGF-β2, or TGF-β2 together with curcumin or rosiglitazone. Cell morphology was assessed at 0, 24, 48, and 72 h. Cur, curcumin; Rosi, rosiglitazone.
FIGURE 3
FIGURE 3
Curcumin potently inhibits TGF-β2 induced secretion of collagen I. Mouse lung fibroblasts were treated with 10 ng/ml TGF-β2 alone or after pretreatment with 50 μM curcumin or 40 μM rosiglitazone, and the secretion of collagen I was determined by ELISA. #Significant increase after TGF-β2 treatment compared with control (P < 0.05, ANOVA).∗Significant reduction after curcumin or rosiglitazone treatment compared with TGF-β2 alone (P < 0.05, ANOVA). Cur, curcumin; Rosi, rosiglitazone.
FIGURE 4
FIGURE 4
Curcumin inhibits TGF-β2 induced α-SMA expression. Mouse lung fibroblasts were pretreated with curcumin (50 μM) or rosiglitazone (40 μM) for 2 h and then treated with TGF-β2 (10 ng/ml) for 24 h. Immunocytochemical analysis for α-SMA (green, middle panel) was performed, DAPI (blue, left panel) was used to visualize the nuclei, and merged images were shown in right panel. Cur, curcumin; Rosi, rosiglitazone. Bar: 20 μm.
FIGURE 5
FIGURE 5
Curcumin upregulates peroxisome proliferator-activated receptor gamma (PPAR-γ) and downregulates PDGFR-β during TGF-β2-induced myofibroblast differentiation. (A) Mouse fibroblasts were treated for 24 h with TGF-β2 alone or together with 0–50 μM Cur. PPAR-γ, PDGFR-β, and FGFR1 mRNA levels were detected by PCR and normalized to β-actin mRNA. ∗P < 0.05, ANOVA. (B) Mouse fibroblasts were treated for 24 h with TGF-β2 alone or together with 0–40 μM Rosi. PPAR-γ, PDGFR-β, and FGFR1 mRNA levels were detected by PCR and normalized to β-actin mRNA. ∗P < 0.05, ANOVA. (C) Western blot analysis of PPAR-γ protein expression. ∗P < 0.05, ∗∗P < 0.05, #P < 0.05, ANOVA. (D) Western blot analysis of PDGFR-β protein expression. ∗P < 0.05, ∗∗P < 0.05, ANOVA. (E) Western blot analysis of FGFR1 protein expression. ∗∗P < 0.05, ns P > 0.05, ANOVA. β-actin was loading control. Cur, Curcumin; Rosi, rosiglitazone.
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