astaxanthine and Pulmonary-Fibrosis

Promotion of myofibroblast apoptosis is a potential therapeutic strategy for pulmonary fibrosis. This study investigated the antifibrotic effect of astaxanthin on the promotion of myofibroblast apoptosis based on dynamin-related protein-1 (Drp1)-mediated mitochondrial fission in vivo and in vitro. Results showed that astaxanthin can inhibit lung parenchymal distortion and collagen deposition, as well as promote myofibroblast apoptosis. Astaxanthin demonstrated pro-apoptotic function in myofibroblasts by contributing to mitochondrial fission, thereby leading to apoptosis by increasing the Drp1 expression and enhancing Drp1 translocation into the mitochondria. Two specific siRNAs were used to demonstrate that Drp1 is necessary to promote astaxanthin-induced mitochondrial fission and apoptosis in myofibroblasts. Drp1-associated genes, such as Bcl-2-associated X protein, cytochrome c, tumour suppressor gene p53 and p53-up-regulated modulator of apoptosis, were highly up-regulated in the astaxanthin group compared with those in the sham group. This study revealed that astaxanthin can prevent pulmonary fibrosis by promoting myofibroblast apoptosis through a Drp1-dependent molecular pathway. Furthermore, astaxanthin provides a potential therapeutic value in pulmonary fibrosis treatment.

Topics: Animals; Apoptosis; Apoptosis Regulatory Proteins; bcl-2-Associated X Protein; Cell Count; Cell Line, Tumor; Disease Models, Animal; Dynamins; Gene Expression Regulation, Neoplastic; GTP Phosphohydrolases; Humans; Microtubule-Associated Proteins; Mitochondrial Dynamics; Mitochondrial Proteins; Myofibroblasts; Protein Transport; Proto-Oncogene Proteins; Pulmonary Fibrosis; Rats, Sprague-Dawley; Tumor Suppressor Protein p53; Xanthophylls

Astaxanthin, a member of the carotenoid family, is the only known ketocarotenoid transported into the brain by transcytosis through the blood-brain barrier. However, whether astaxanthin has antifibrotic functions is unknown. In this study, we investigated the effects of astaxanthin on transforming growth factor β1-mediated and bleomycin-induced pulmonary fibrosis in vitro and in vivo. The results showed that astaxanthin significantly improved the structure of the alveoli and alleviated collagen deposition in vivo. Compared with the control group, the astaxanthin-treated groups exhibited downregulated protein expressions of α-smooth muscle actin, vimentin, hydroxyproline, and B cell lymphoma/leukemia-2 as well as upregulated protein expressions of E-cadherin and p53 in vitro and in vivo. Astaxanthin also inhibited the proliferation of activated A549 and MRC-5 cells at median inhibitory concentrations of 40 and 30 μM, respectively. In conclusion, astaxanthin could relieve the symptoms and halt the progression of pulmonary fibrosis, partly by preventing transdifferentiation, inhibiting proliferation, and promoting apoptosis of activated cells.

Topics: Actins; Antigens, CD; Apoptosis; Bleomycin; Blood-Brain Barrier; Cadherins; Cell Line, Tumor; Cell Proliferation; Cell Transdifferentiation; Collagen; Down-Regulation; Humans; Hydroxyproline; Lung; Microscopy, Electron, Transmission; Pulmonary Alveoli; Pulmonary Fibrosis; Transforming Growth Factor beta1; Tumor Suppressor Protein p53; Up-Regulation; Vimentin; Xanthophylls