Fig. 5
d-Limonene inhibited lung cancer progression and pulmonary fibrosis by attenuating lipid metabolism disorder caused by PM2.5 exposure. A The expression of miR-195 increased after treatment with d-limonene. B Dual luciferase experiments showed the binding of miR-195 with SREBF1, FASN and ACACA mRNAs. C The protein expression of SREBP1, FASN and ACACA was inhibited by miR-195. D Western blot analysis showed that SREBP1, FASN and ACACA upregulated by PM2.5 exposure were attenuated by d-limonene or miR-195 treatment. E, F Plate colony formation and Transwell experiments showed that PM2.5-induced proliferation and invasion of lung cancer cells were inhibited by d-limonene or miR-195 treatment. G, H The upregulation of SREBF1, ACACA and FASN by PM2.5 in miR-195 KO mice was attenuated after d-limonene treatment (G), and the attenuation was more evident in WT mice (H). I Masson’s trichrome staining showed that d-limonene repaired the fibrosis caused by PM2.5 exposure, and the level of pulmonary fibrosis in miR-195 KO mice treated with d-limonene was significantly higher than that of WT mice (N = 6). J, K Western blot analysis showed that PM2.5-induced upregulation of collagen I and vimentin was inhibited by d-limonene in WT and miR-195 KO mice (N = 4, 5, 4, separately). *P < 0.05; **P < 0.01; ***P < 0.001. MPM: miR-195 KO mice − PM2.5 exposure group. MPD: miR-195 KO mice − PM2.5 exposure + d-limonene group. CPD: C57BL/6J mice − PM2.5 exposure + d-limonene group