RESUMO
OBJECTIVE: To explore the effect of curcumin on TGF-ß2 regulated peroxisome proliferater activated receptor y (PPAR-γ)/platelet derived growth factor ß (PDGF-ß) signaling pathway in lung fibroblasts of mice. METHODS: C57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-ß2, curcumin, or TGF-ß2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 µmol/L), the TGF-ß2 (10 ng/mL) group, TGF-ß2 (10 ng/mL) plus curcumin (5, 25, 50 µmol/L) groups. mRNA expressions of PPAR-γ, platelet-derived growth factor receptor ß (PDGFR-ß), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-γ and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-ß2 group, the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group. RESULTS: Compared with the blank control group, curcumin 50 µmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-ß2 group, TGF-ß2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-γ and PDGF-ß, as well as protein expression of PPAR-γ increased, the collagen-1 expression also increased in the TGF-ß2 group (P < 0.05). Compared with the TGF-ß2 group, mRNA expressions of PPAR-γ obviously increased in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group, higher than that in the TGF-ß2 (10 ng/mL) plus curcumin 5 [µmol/L group (P < 0.05). mRNA expressions of PPAR-γ was higher in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). mRNA expressions of PDGF-ß was lower in TGF-ß2 (10 ng/mL) plus curcumin groups than in the TGF-ß2 group (P < 0.05). Besides, PDGF-ß mRNA expressions were lower in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 5 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-ß2 group and 3 TGF-ß2 plus curcumin groups (P > 0.05). Compared with the TGF-ß2 group, PPAR-γ protein expressions increased and collagen-1 protein expressions decreased in the TGF-ß2 (10 ng/mL) plus curcumin 50 µLmol/L group (P < 0.05, P < 0.01). CONCLUSIONS: Curcumin not only could inhibit TGF-ß2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-γ expressions and down-regulating PDGF-ß expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-γ/PDGF-ß signaling pathway.