title: Essential roles for early growth response transcription factor Egr-1 in tissue fibrosis and wound healing.
abstract: The early growth response gene (Egr-1) codes for a zinc finger transcription factor that has important roles in the regulation of cell growth, differentiation, and survival. Aberrant Egr-1 expression is implicated in carcinogenesis, inflammation, atherosclerosis, and ischemic injury. We reported previously that normal fibroblasts stimulated by transforming growth factor-ss showed rapid and transient induction of Egr-1. Moreover, we observed that tissue expression of Egr-1 was elevated in patients with scleroderma, which suggests that Egr-1 may be involved in tissue repair and fibrosis. Here, we investigated matrix remodeling and wound healing in mice harboring gain of function or loss of function mutations of Egr-1. Using the model of bleomycin-induced scleroderma, we found that the early influx of inflammatory cells into the skin and lungs, and the subsequent development of fibrosis in these organs, were markedly attenuated in Egr-1 null mice. Furthermore, full-thickness incisional skin wound healing was impaired, and skin fibroblasts lacking Egr-1 showed reduced migration and myofibroblast transdifferentiation in vitro. In contrast, transgenic mice with fibroblast-specific Egr-1 overexpression showed exuberant tissue repair, with enhanced collagen accumulation and increased tensile strength of incisional wounds. Together, these results point to the fundamental role that Egr-1 plays in the regulation of transforming growth factor-ss-dependent physiological and pathological matrix remodeling.
authors.affiliation: Division of Rheumatology, Feinberg School of Medicine, Northwestern University, 240 E Huron St., Chicago, IL 60611, USA.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wu
authors.forename: Denisa S
authors.initials: DS
authors.lastname: Melichian
authors.forename: Mauricio
authors.initials: M
authors.lastname: de la Garza
authors.forename: Katherine
authors.initials: K
authors.lastname: Gruner
authors.forename: Swati
authors.initials: S
authors.lastname: Bhattacharyya
authors.forename: Luke
authors.initials: L
authors.lastname: Barr
authors.forename: Aisha
authors.initials: A
authors.lastname: Nair
authors.forename: Shiva
authors.initials: S
authors.lastname: Shahrara
authors.forename: Peter H S
authors.initials: PH
authors.lastname: Sporn
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Mustoe
authors.forename: Warren G
authors.initials: WG
authors.lastname: Tourtellotte
authors.forename: John
authors.initials: J
authors.lastname: Varga
mesh_terms: D000818:Animals; D001761:Bleomycin / Q000009:adverse effects; D002454:Cell Differentiation / Q000235:genetics; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D003094:Collagen; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012871:Skin Diseases / Q000139:chemically induced / Q000235:genetics / Q000473:pathology*; D014945:Wound Healing / Q000235:genetics*
chemical_list: D051766:Early Growth Response Protein 1; D001761:Bleomycin; D003094:Collagen
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