Matrix metalloproteinase-7 coordinates airway epithelial injury response and differentiation of ciliated cells

Sina A. Gharib, William A. Altemeier, Laura S. Van Winkle, Charles Plopper, Saundra Y. Schlesinger, Catherine A. Buell, Rena Brauer, Vivian Lee, William C. Parks, Peter Chen

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Matrix metalloproteinase-7 (MMP7) expression is quickly upregulated 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.

Original languageEnglish (US)
Pages (from-to)390-396
Number of pages7
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume48
Issue number3
DOIs
StatePublished - Mar 2013

Keywords

  • Matrilysin
  • Microarray
  • MMP7
  • Wound repair

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry

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    Gharib, S. A., Altemeier, W. A., Van Winkle, L. S., Plopper, C., Schlesinger, S. Y., Buell, C. A., Brauer, R., Lee, V., Parks, W. C., & Chen, P. (2013). Matrix metalloproteinase-7 coordinates airway epithelial injury response and differentiation of ciliated cells. American Journal of Respiratory Cell and Molecular Biology, 48(3), 390-396. https://doi.org/10.1165/rcmb.2012-0083OC