| First Author | Zhu C | Year | 2023 |
| Journal | Aging Cell | Volume | 22 |
| Issue | 4 | Pages | e13790 |
| PubMed ID | 36794355 | Mgi Jnum | J:353329 |
| Mgi Id | MGI:7462677 | Doi | 10.1111/acel.13790 |
| Citation | Zhu C, et al. (2023) Role of pulmonary epithelial arginase-II in activation of fibroblasts and lung inflammaging. Aging Cell 22(4):e13790 |
| abstractText | Elevated arginases including type-I (Arg-I) and type-II isoenzyme (Arg-II) are reported to play a role in aging, age-associated organ inflammaging, and fibrosis. A role of arginase in pulmonary aging and underlying mechanisms are not explored. Our present study shows increased Arg-II levels in aging lung of female mice, which is detected in bronchial ciliated epithelium, club cells, alveolar type 2 (AT2) pneumocytes, and fibroblasts (but not vascular endothelial and smooth muscle cells). Similar cellular localization of Arg-II is also observed in human lung biopsies. The age-associated increase in lung fibrosis and inflammatory cytokines, including IL-1beta and TGF-beta1 that are highly expressed in bronchial epithelium, AT2 cells, and fibroblasts, are ameliorated in arg-ii deficient (arg-ii(-/-) ) mice. The effects of arg-ii(-/-) on lung inflammaging are weaker in male as compared to female animals. Conditioned medium (CM) from human Arg-II-positive bronchial and alveolar epithelial cells, but not that from arg-ii(-/-) cells, activates fibroblasts to produce various cytokines including TGF-beta1 and collagen, which is abolished by IL-1beta receptor antagonist or TGF-beta type I receptor blocker. Conversely, TGF-beta1 or IL-1beta also increases Arg-II expression. In the mouse models, we confirmed the age-associated increase in IL-1beta and TGF-beta1 in epithelial cells and activation of fibroblasts, which is inhibited in arg-ii(-/-) mice. Taken together, our study demonstrates a critical role of epithelial Arg-II in activation of pulmonary fibroblasts via paracrine release of IL-1beta and TGF-beta1, contributing to pulmonary inflammaging and fibrosis. The results provide a novel mechanistic insight in the role of Arg-II in pulmonary aging. |
