| First Author | Fang F | Year | 2011 |
| Journal | Am J Pathol | Volume | 178 |
| Issue | 5 | Pages | 2077-90 |
| PubMed ID | 21514423 | Mgi Jnum | J:171591 |
| Mgi Id | MGI:4950609 | Doi | 10.1016/j.ajpath.2011.01.035 |
| Citation | Fang F, et al. (2011) The Early Growth Response Gene Egr2 (Alias Krox20) Is a Novel Transcriptional Target of Transforming Growth Factor-beta that Is Up-Regulated in Systemic Sclerosis and Mediates Profibrotic Responses. Am J Pathol 178(5):2077-90 |
| abstractText | Although the early growth response-2 (Egr-2, alias Krox20) protein shows structural and functional similarities to Egr-1, these two related early-immediate transcription factors are nonredundant. Egr-2 plays essential roles in peripheral nerve myelination, adipogenesis, and immune tolerance; however, its regulation and role in tissue repair and fibrosis remain poorly understood. We show herein that transforming growth factor (TGF)-beta induced a Smad3-dependent sustained stimulation of Egr2 gene expression in normal fibroblasts. Overexpression of Egr-2 was sufficient to stimulate collagen gene expression and myofibroblast differentiation, whereas these profibrotic TGF-beta responses were attenuated in Egr-2-depleted fibroblasts. Genomewide transcriptional profiling revealed that multiple genes associated with tissue remodeling and wound healing were up-regulated by Egr-2, but the Egr-2-regulated gene expression profile overlapped only partially with the Egr-1-regulated gene profile. Levels of Egr-2 were elevated in lesional tissue from mice with bleomycin-induced scleroderma. Moreover, elevated Egr-2 was noted in biopsy specimens of skin and lung from patients with systemic sclerosis. These results provide the first evidence that Egr-2 is a functionally distinct transcription factor that is both necessary and sufficient for TGF-beta-induced profibrotic responses and is aberrantly expressed in lesional tissue in systemic sclerosis and in a murine model of scleroderma. Together, these findings suggest that Egr-2 plays an important nonredundant role in the pathogenesis of fibrosis. Targeting Egr-2 might represent a novel therapeutic strategy to control fibrosis. |
