Induction of Arginase I and II in Bleomycin-induced Fibrosis of Mouse Lung
Overview
Molecular Biology
Physiology
Pulmonary Medicine
Authors
Affiliations
Arginase, which hydrolyzes arginine to urea and ornithine, is a precursor for the synthesis of polyamines and proline, which is abundant in collagen. The supply of proline can be a crucial factor in the process of lung fibrosis. We investigated the induction of arginine metabolic enzymes in bleomycin-induced mouse lung fibrosis. Histological studies and quantification of lung hydroxyproline showed that lung fibrosis develops in up to 14 days after bleomycin treatment. Under these conditions, collagen I mRNA was induced gradually in up to 15 days, and the content of hydroxyproline reached a maximum at 10 days. Arginase I mRNA was undetectable before bleomycin treatment but was induced 5-10 days after this treatment. Arginase I protein was induced at 7 days and remained little changed for up to 10 days and decreased at 14 days. On the other hand, arginase II mRNA that was detectable before treatment was increased gradually for up to 10 days and decreased at 14 days. Arginase II protein began to increase at day 5, increased for up to 10 days, and was decreased at day 14. mRNAs for cationic amino acid transporter-2 and ornithine decarboxylase were induced in a manner similar to that seen with collagen I mRNA. Immunohistochemical analysis showed that arginase I is induced in macrophages, whereas arginase II is induced in various cell types, including macrophages and myofibroblasts, and roughly colocalizes with the collagen-specific chaperone heat shock protein 47. Our findings suggest that arginine metabolic enzymes play an important role in the development of lung fibrosis, at least in mice.
The Therapeutic Potential of Myo-Inositol in Managing Patients with Respiratory Diseases.
Quecchia C, Vianello A Int J Mol Sci. 2025; 26(5).
PMID: 40076806 PMC: 11901072. DOI: 10.3390/ijms26052185.
Pan C, Wei H, Chen B, Wu L, Song J, Zhang Q J Transl Med. 2024; 22(1):1058.
PMID: 39587675 PMC: 11587652. DOI: 10.1186/s12967-024-05895-0.
Role of Arginine and its Metabolism in TGF-β-Induced Activation of Lung Fibroblasts.
Hamanaka R, Shin K, Atalay M, Cetin-Atalay R, Shah H, Szafran J bioRxiv. 2024; .
PMID: 39554075 PMC: 11565920. DOI: 10.1101/2024.11.01.618293.
A pilot metabolomics study across the continuum of interstitial lung disease fibrosis severity.
Zhan J, Jarrell Z, Hu X, Weinberg J, Orr M, Marts L Physiol Rep. 2024; 12(20):e70093.
PMID: 39424430 PMC: 11489002. DOI: 10.14814/phy2.70093.
Jiang H, Zheng B, Hu G, Kuang L, Zhou T, Li S J Pharm Anal. 2024; 14(9):100971.
PMID: 39381647 PMC: 11459407. DOI: 10.1016/j.jpha.2024.100971.