1. Anti-Fibrotic Effects of Low Toxic Microcystin-RR on Bleomycin-Induced Pulmonary Fibrosis: A Comparison with Microcystin-LR
- Author
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Jie Wang, Yan Ren, Xiufen Zheng, Jiaqi Kang, Zhenqian Huang, Lizhi Xu, and Yaping Wang
- Subjects
0301 basic medicine ,Vimentin ,SMAD ,RM1-950 ,Bleomycin ,Extracellular matrix ,03 medical and health sciences ,Idiopathic pulmonary fibrosis ,chemistry.chemical_compound ,0302 clinical medicine ,Pulmonary fibrosis ,medicine ,Pharmacology (medical) ,Original Research ,Pharmacology ,biology ,pulmonary fibrosis ,microcystin-LR ,bleomycin ,business.industry ,microcystin-RR ,medicine.disease ,macrophages ,Fibronectin ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Cancer research ,Therapeutics. Pharmacology ,business ,Transforming growth factor - Abstract
Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial pulmonary disease characterized with radiographically evident pulmonary infiltrates and extracellular matrix deposition with limited treatment options. We previously described that microcystin-LR (MC-LR) reduces transforming growth factor (TGF)-β1/Smad signaling and ameliorates pulmonary fibrosis in bleomycin (BLM)-induced rat models. In the present study, we further demonstrate that microcystin-RR (MC-RR), an MC congener with lower toxicity than MC-LR, exerted an anti-fibrotic effect on BLM-induced pulmonary fibrosis rodent models and compared it with MC-LR. Our data show that MC-RR treatment attenuated BLM-associated pulmonary inflammation and collagen deposition in both therapeutic and preventive models. MC-RR reduced the expression of fibrotic markers, including vimentin, α-smooth muscle actin, collagen 1α1, and fibronectin, in rat pulmonary tissues. Furthermore, the core features of BLM-induced pulmonary fibrotic lesions were better alleviated by MC-RR than by MC-LR. MC-RR treatment substantially decreased the number of pulmonary M2 macrophages. In vitro, MC-RR attenuated the epithelial-mesenchymal transition and fibroblast-myofibroblast transition triggered by M2 macrophages. Therefore, we highlight MC-RR as a promising molecule for developing therapeutic and prophylactic strategies against IPF, a refractory lung disease.
- Published
- 2021