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We hypothesized that CCAAT\/enhancer binding protein\u2013\u03b1 (C\/EBP\u03b1), a transcription factor critical for perinatal lung maturation, regulates genes required for the normal repair of the bronchiolar epithelium after injury. Transgenic Cebp\u03b1\u0394\/\u0394 mice, in which Cebpa was conditionally deleted from Clara cells and Type II cells after birth, were used in this study. Airway injury was induced in mice by the intraperitoneal administration of naphthalene to ablate bronchiolar epithelial cells. Although the deletion of C\/EBP\u03b1 did not influence lung structure and function under unstressed conditions, C\/EBP\u03b1 was required for the normal repair of terminal bronchiolar epithelium after naphthalene injury. To identify cellular processes that are influenced by C\/EBP\u03b1 during repair, mRNA microarray was performed on terminal bronchiolar epithelial cells isolated by laser-capture microdissection. Normal repair of the terminal bronchiolar epithelium was highly associated with the mRNAs regulating antiprotease activities, and their induction required C\/EBP\u03b1. The defective deposition of fibronectin in Cebp\u03b1\u0394\/\u0394 mice was associated with increased protease activity and delayed differentiation of FoxJ1-expressing ciliated cells. The fibronectin and ciliated cells were restored by the intratracheal treatment of Cebp\u03b1\u0394\/\u0394 mice with the serine protease inhibitor. In conclusion, C\/EBP\u03b1 regulates the expression of serine protease inhibitors that are required for the normal increase of fibronectin and the restoration of ciliated cells after injury. Treatment with serine protease inhibitor may aid in the recovery of injured bronchiolar epithelial cells, and prevent common chronic lung diseases.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0239oc","type":"journal-article","created":{"date-parts":[[2012,6,7]],"date-time":"2012-06-07T18:40:40Z","timestamp":1339094440000},"page":"454-463","source":"Crossref","is-referenced-by-count":17,"title":["CCAAT\/Enhancer Binding Protein\u2013\u03b1 Regulates the Protease\/Antiprotease Balance Required for Bronchiolar Epithelium Regeneration"],"prefix":"10.1093","volume":"47","author":[{"given":"Atsuyasu","family":"Sato","sequence":"first","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Xu","sequence":"additional","affiliation":[{"name":"Division of Pulmonary Biology, Cincinnati Children\u2019s Hospital Medical Center, 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