title: Matrix metalloproteinase-7 coordinates airway epithelial injury response and differentiation of ciliated cells.
abstract: Matrix metalloproteinase-7 (MMP7) expression is quickly up-regulated after injury, and functions to regulate wound repair and various mucosal immune processes. We evaluated the global transcriptional response of airway epithelial cells from wild-type and Mmp7-null mice cultured at an air-liquid interface. The analysis of differentially expressed genes between genotypes after injury revealed an enrichment of functional categories associated with inflammation, cilia, and differentiation. Because these analyses suggested that MMP7 regulated ciliated cell formation, we evaluated the recovery of the airway epithelium in wild-type and Mmp7-null mice in vivo after naphthalene injury, which revealed augmented ciliated cell formation in the absence of MMP7. Moreover, in vitro studies evaluating cell differentiation in air-liquid interface cultures also showed faster ciliated cell production under Mmp7-null conditions compared with wild-type conditions. These studies identified a new role for MMP7 in attenuating ciliated cell differentiation during wound repair.
authors.affiliation: Center for Lung Biology, University of Washington, 850 Republican Street, Seattle, WA 98109, USA. sagharib@uw.edu
authors.forename: Sina A
authors.initials: SA
authors.lastname: Gharib
authors.forename: William A
authors.initials: WA
authors.lastname: Altemeier
authors.forename: Laura S
authors.initials: LS
authors.lastname: Van Winkle
authors.forename: Charles G
authors.initials: CG
authors.lastname: Plopper
authors.forename: Saundra Y
authors.initials: SY
authors.lastname: Schlesinger
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Buell
authors.forename: Rena
authors.initials: R
authors.lastname: Brauer
authors.forename: Vivian
authors.initials: V
authors.lastname: Lee
authors.forename: William C
authors.initials: WC
authors.lastname: Parks
authors.forename: Peter
authors.initials: P
authors.lastname: Chen
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology*; D015870:Gene Expression; D005838:Genotype; D055370:Lung Injury / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D020545:Respiratory Mucosa / Q000201:enzymology / Q000293:injuries* / Q000294:innervation* / Q000473:pathology / Q000503:physiopathology*; D014158:Transcription, Genetic; D059467:Transcriptome; D015854:Up-Regulation; D014945:Wound Healing / Q000235:genetics* / Q000502:physiology
chemical_list: C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7