Differential expression of extracellular matrix metalloproteinase inducer (CD147) in normal and ulcerated corneas: Role in epithelio-stromal interactions and matrix metalloproteinase induction

Eric E. Gabison, Samia Mourah, Emanuelle Steinfels, Li Yan, Thanh Hoang-Xuan, Mitchel A. Watsky, Bart De Wever, Fabien Calvo, Alain Mauviel, Suzanne Menashi

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN) was originally identified on the tumor cell surface as an inducer of matrix metalloproteinase (MMP) production in neighboring fibroblasts. Here we demonstrate a role for EMMPRIN in MMP induction during corneal wound healing. MMP and EMMPRIN expression was analyzed in normal and ulcerated human corneas, as well as in corneal epithelial and stromal cells in culture using confocal microscopy, zymography, immunoblots, and realtime polymerase chain reaction. In normal cornea EMMPRIN was predominantly expressed in the epithelium but was markedly induced in the anterior stroma of ulcerated corneas. This coincided with MMP-2 induction that co-localized with EMMPRIN at the epithelo-stromal boundary. The role of epithelial-stromal interaction in MMP induction was investigated in an in vitro co-culture system and demonstrated an induction and co-localization of EMMPRIN and MMP-2 in the fibroblasts at the interface with epithelial cells. Direct contact of fibroblasts with EMMPRIN-containing purified epithelial cell membranes also induced MMP-1, MMP-2, and EMMPRIN and this was inhibited by a blocking anti-EMMPRIN antibody, suggesting that EMMPRIN was primarily responsible for this induction. These findings, and the up-regulation of EMMPRIN by epidermal growth factor and transforming growth factor-β, demonstrate a role for EMMPRIN in wound healing and suggest that sustained local up-regulation of EMMPRIN and MMPs in chronic situations in which healing is delayed may lead to excessive matrix degradation and corneal melts.

Original languageEnglish (US)
Pages (from-to)209-219
Number of pages11
JournalAmerican Journal of Pathology
Volume166
Issue number1
DOIs
StatePublished - Jan 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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