| First Author | Kawara A | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 16490 |
| PubMed ID | 33020583 | Mgi Jnum | J:299077 |
| Mgi Id | MGI:6472385 | Doi | 10.1038/s41598-020-73752-3 |
| Citation | Kawara A, et al. (2020) Spred2-deficiency enhances the proliferation of lung epithelial cells and alleviates pulmonary fibrosis induced by bleomycin. Sci Rep 10(1):16490 |
| abstractText | The mitogen-activated protein kinase (MAPK) pathways are involved in many cellular processes, including the development of fibrosis. Here, we examined the role of Sprouty-related EVH-1-domain-containing protein (Spred) 2, a negative regulator of the MAPK-ERK pathway, in the development of bleomycin (BLM)-induced pulmonary fibrosis (PF). Compared to WT mice, Spred2(-/-) mice developed milder PF with increased proliferation of bronchial epithelial cells. Spred2(-/-) lung epithelial cells or MLE-12 cells treated with spred2 siRNA proliferated faster than control cells in vitro. Spred2(-/-) and WT macrophages produced similar levels of TNFalpha and MCP-1 in response to BLM or lipopolysaccharide and myeloid cell-specific deletion of Spred2 in mice had no effect. Spred2(-/-) fibroblasts proliferated faster and produced similar levels of MCP-1 compared to WT fibroblasts. Spred2 mRNA was almost exclusively detected in bronchial epithelial cells of naive WT mice and it accumulated in approximately 50% of cells with a characteristic of Clara cells, 14 days after BLM treatment. These results suggest that Spred2 is involved in the regulation of tissue repair after BLM-induced lung injury and increased proliferation of lung bronchial cells in Spred2(-/-) mice may contribute to faster tissue repair. Thus, Spred2 may present a new therapeutic target for the treatment of PF. |
