Butyrate Prevents TGF-beta 1-Induced Alveolar Myofibroblast Differentiation and Modulates Energy Metabolism
- Abstract
- Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by excessive collagen matrix deposition and extracellular remodeling. Signaling pathways mediated by fibrotic cytokine transforming growth factor beta 1 (TGF-beta 1) make important contributions to pulmonary fibrosis, but it remains unclear how TGF-beta 1 alters metabolism and modulates the activation and differentiation of pulmonary fibroblasts. We found that TGF-beta 1 lowers NADH and NADH/NAD levels, possibly due to changes in the TCA cycle, resulting in reductions in the ATP level and oxidative phosphorylation in pulmonary fibroblasts. In addition, we showed that butyrate (C4), a short chain fatty acid (SCFA), exhibits potent antifibrotic activity by inhibiting expression of fibrosis markers. Butyrate treatment inhibited mitochondrial elongation in TGF-beta 1-treated lung fibroblasts and increased the mitochondrial membrane potential (MMP). Consistent with the mitochondrial observations, butyrate significantly increased ADP, ATP, NADH, and NADH/NAD levels in TGF-beta 1-treated pulmonary fibroblasts. Collectively, our findings indicate that TGF-beta 1 induces changes in mitochondrial dynamics and energy metabolism during myofibroblast differentiation, and that these changes can be modulated by butyrate, which enhances mitochondrial function.
- Author(s)
- Hyo Yeong Lee; 남소미; 김미정; Su Jung Kim; 백승훈; Hyun Ju Yoo
- Issued Date
- 2021
- Type
- Article
- Keyword
- short chain fatty acids; butyrate; TGF-β1; pulmonary fibrosis; myofibroblast differentiation; mitochondria; metabolites
- DOI
- 10.3390/metabo11050258
- URI
- https://oak.ulsan.ac.kr/handle/2021.oak/9569
https://ulsan-primo.hosted.exlibrisgroup.com/primo-explore/fulldisplay?docid=TN_cdi_doaj_primary_oai_doaj_org_article_794e9a84c2f14779b56fedb23b9dcf79&context=PC&vid=ULSAN&lang=ko_KR&search_scope=default_scope&adaptor=primo_central_multiple_fe&tab=default_tab&query=any,contains,Butyrate%20Prevents%20TGF-beta%201-Induced%20Alveolar%20Myofibroblast%20Differentiation%20and%20Modulates%20Energy%20Metabolism&offset=0&pcAvailability=true
- Publisher
- METABOLITES
- Location
- 스위스
- Language
- 영어
- ISSN
- 2218-1989
- Citation Volume
- 11
- Citation Number
- 5
- Citation Start Page
- 258
- Citation End Page
- 258
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- Natural Science > Biological Sciences
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