Differential expression of MMP-2 and -9 and their inhibitors in fetal lung cells exposed to mechanical stretch: Regulation by IL-10

Renda L. Hawwa, Michael A. Hokenson, Yulian Wang, Zheping Huang, Surendra Sharma, Juan Sanchez-Esteban

Research output: Contribution to journalArticlepeer-review

16 Scopus citations

Abstract

Study Objectives: Abnormal remodeling of the extracellular matrix (ECM) has been implicated in the pathogenesis of bronchopulmonary dysplasia. However, the contribution of lung parenchymal cells to ECM remodeling after mechanical injury is not well defined. The objective of these studies was to investigate in vitro the release of MMP-2 and -9 and their respective inhibitors TIMP-2 and -1, and to explore potential regulation by IL-10. Design: Mouse fetal epithelial cells and fibroblasts isolated on E18-19 of gestation were exposed to 20% cyclic stretch to simulate lung injury. MMP-2 and MMP-9 activity were investigated by zymography and ELISA. TIMP-1 and TIMP-2 abundance were analyzed by Western blot. Results: We found that mechanical stretch increased MMP-2 and decreased TIMP-2 in fibroblasts, indicating that excessive stretch promotes MMP-2 activation, expressed as the MMP-2/TIMP-2 ratio. Incubation with IL-10 did not change MMP-2 activity. In contrast, mechanical stretch of epithelial cells decreased MMP-9 activity and the MMP-9/TIMP-1 ratio by 60-70%. When IL-10 was added, mechanical stretch increased the MMP-9/TIMP-1 ratio by 50%. Conclusions: We conclude that mechanical stretch differentially affects MMP-2/9 and their inhibitors in fetal lung cells. IL-10 modulates MMP-9 activity through a combination of effects on MMP-9 and TIMP-1 levels.

Original languageEnglish (US)
Pages (from-to)341-349
Number of pages9
JournalLung
Volume189
Issue number4
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • Bronchopulmonary dysplasia
  • Epithelial cells
  • Fibroblasts
  • Matrix metalloproteinases
  • Mechanical injury
  • TIMP-1/2

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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