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- Title
The Inhibitory Effects of Cyclodepsipeptides from the Entomopathogenic Fungus Beauveria bassiana on Myofibroblast Differentiation in A549 Alveolar Epithelial Cells.
- Authors
Park, Yong Joo; Lee, Seoung Rak; Kim, Dong Min; Yu, Jae Sik; Beemelmanns, Christine; Chung, Kyu Hyuck; Kim, Ki Hyun
- Abstract
Pulmonary fibrosis (PF) is a chronic and fatal lung disease with few treatment options. Although the pathogenesis of PF is not clear, a chronic inflammatory response to continuous damage is considered the cause of pulmonary fibrosis. PF is characterized by excessive accumulation of extracellular matrix (ECM), therefore, inhibition of myofibroblast differentiation is a good therapeutic target for PF. As part of our continuing endeavor to explore biologically active metabolites from insect-associated microbes, we found that the MeOH extract of the culture broth from the entomopathogenic fungus Beauveria bassiana inhibited collagen induction and E-cadherin down-regulation. In order to identify active compounds, we carried out chemical analysis of the MeOH extract with the assistance of LC/MS-guided isolation approach, which led to the successful identification of four cyclodepsipeptides 1–4. Among the isolates, compound 2 showed inhibitory effects on myofibroblast differentiation induced by TGF-β1. Compound 2 inhibited induction of α-SMA and N-cadherin, which are myofibroblast markers, and blocked the accumulation of ECM proteins such as collagen and fibronectin. Overall these findings demonstrate that compound 2 can be used to attenuate pulmonary fibrosis by targeting myo- fibroblast differentiation.
- Subjects
PULMONARY fibrosis; LUNG diseases; EXTRACELLULAR matrix; MYOFIBROBLASTS; MICROORGANISMS; BEAUVERIA bassiana
- Publication
Molecules, 2018, Vol 23, Issue 10, p2568
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23102568