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

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.