Role of Arginine and its Metabolism in TGF-β-Induced Activation of Lung Fibroblasts.

ABSTRACT: Arginine is a conditionally essential amino acid with known roles in protein production, nitric oxide synthesis, biosynthesis of proline and polyamines, and regulation of intracellular signaling pathways. Arginine biosynthesis and catabolism have been linked to TGF-β-induced activation of fibroblasts in the context of pulmonary fibrosis; however, a thorough study on the metabolic and signaling roles of arginine in the process of fibroblast activation has not been conducted. Here, we used metabolic dropouts and labeling strategies to determine how activated fibroblasts utilize arginine. We found that arginine limitation leads to activation of GCN2 while inhibiting TGF-β-induced mTORC1 activation and collagen protein production. Extracellular citrulline could rescue the effect of arginine de

SUBMITTER: Hamanaka RB 

PROVIDER: S-EPMC11565920 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature