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Butyrate Prevents TGF-beta 1-Induced Alveolar Myofibroblast Differentiation and Modulates Energy Metabolism

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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 Lee남소미김미정Su Jung Kim백승훈Hyun Ju Yoo
Issued Date
2021
Type
Article
Keyword
short chain fatty acidsbutyrateTGF-β1pulmonary fibrosismyofibroblast differentiationmitochondriametabolites
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
Appears in Collections:
Natural Science > Biological Sciences
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