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Targeting branched-chain amino acids alleviates pulmonary fibrosis [CUT&Tag]

ABSTRACT: Purpose: We previously observed significant dysregulation in the expression of key BCAA metabolic genes during idiopathic pulmonary fibrosis (IPF). This study aims to elucidate the molecular mechanisms underlying BCAA metabolic genes dysregulation during IPF progression. Methods: ATF4 CUT&Tag were performed in MLFs and PPARγ CUT&Tag were performed in MLFs treated with TGF-β1 (20 ng/mL) for 48 h. Conclusions: ATF4 and PPARγ respectively regulate the expression of Slc7a5 and BCAA catabolic genes in primary mouse lung fibroblasts (MLFs)

ORGANISM(S): Mus musculus

PROVIDER: GSE295424 | GEO | 2026/03/17

REPOSITORIES: GEO

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Targeting branched-chain amino acids alleviates pulmonary fibrosis [CUT&Tag, histone_modification]

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Targeting branched-chain amino acids alleviates pulmonary fibrosis [RNA-seq]

Project description:Purpose: Previous studies demonstrated that BCAA metabolic reprogramming induces idiopathic pulmonary fibrosis (IPF). This study investigates BCAA-mediated gene expression regulation in primary mouse lung fibroblasts (MLFs). Methods: In vitro: MLFs were cultured in three media conditions: complete medium (Complete), BCAA-free medium (Free), or BCAA-free medium supplemented with BCAAs (Free+BCAA) or BCKA (Free+BCKA) for 24 hours prior to TGF-β1 (20 ng/mL) stimulation for 48 hours. Triplicate RNA-seq analyses were conducted on treated MLFs. In vivo: Comparative RNA-seq profiling was performed on lung tissues from three experimental groups: PBS-treated controls, bleomycin (BLM)-exposed mice, and BLM-treated mice receiving BCAA supplementation (3 mmol/L in drinking water) or BCAA-free diets or BT2 treatment. Conclusions: BCAA metabolism is essential for myofibroblast activation and mechanistically promotes lung fibrogenesis in both in vitro and in vivo models.

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Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder

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Reprograming of Proteasomal Degradation by Branched Chain Amino Acid Metabolism

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