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Recent studies identify the multifunctional transcription factor early growth response\u20101(Egr\u20101) as an important mediator of fibroblast activation triggered by diverse stimuli. Egr\u20101 has potent stimulatory effects on fibrotic gene expression, and aberrant Egr\u20101 expression or function is associated with animal models of fibrosis and human fibrotic disorders, including emphysema, pulmonary fibrosis, pulmonary hypertension and systemic sclerosis. Pharmacological suppression or genetic targeting of Egr\u20101 blocks fibrotic responses <jats:italic>in vitro<\/jats:italic> and ameliorates experimental fibrosis in the skin and lung. In contrast, Egr\u20101 appears to act as a negative regulator of hepatic fibrosis in mouse models, suggesting a context\u2010dependent role in fibrosis. The Egr\u20101\u2010binding protein Nab2 is an endogenous inhibitor of Egr\u20101\u2010mediated signalling and abrogates the stimulation of fibrotic responses induced by transforming growth factor\u2010<jats:italic>\u03b2<\/jats:italic> (<jats:styled-content style=\"fixed-case\">TGF<\/jats:styled-content><jats:italic>\u03b2<\/jats:italic>). Moreover, mice deficient in Nab2 show excessive collagen accumulation in the skin. These observations highlight a previously unsuspected fundamental physiological function for the Egr\u20101\u2013Nab2 signalling axis in regulating fibrogenesis, and suggest that Egr\u20101 may be a potential novel therapeutic target in human diseases complicated by fibrosis. This review summarizes recent advances in understanding the regulation and complex functional role of Egr\u20101 and its related proteins and inhibitors in pathological fibrosis.<\/jats:bold><\/jats:p>","DOI":"10.1002\/path.4131","type":"journal-article","created":{"date-parts":[[2012,11,6]],"date-time":"2012-11-06T10:21:05Z","timestamp":1352197265000},"page":"286-297","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":156,"title":["Egr\u20101: new conductor for the tissue repair orchestra directs harmony (regeneration) or cacophony (fibrosis)"],"prefix":"10.1002","volume":"229","author":[{"given":"Swati","family":"Bhattacharyya","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Northwestern University Feinberg School of Medicine  Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Fang","sequence":"additional","affiliation":[{"name":"Division 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