Cytokines and signaling pathways regulating matrix metalloproteinase‐9 (MMP‐9) expression in corneal epithelial cells
- 22 July 2009
- journal article
- research article
- Published by Wiley in Journal of Cellular Physiology
- Vol. 221 (2), 402-411
- https://doi.org/10.1002/jcp.21869
Abstract
Matrix metalloproteinase‐9 (MMP‐9) is a well‐known regulator and effecter of many cellular processes including wound healing. In the cornea, either too much or too little MMP‐9 can be detrimental to overall wound repair. We investigated the secreted factors as well as the intracellular signaling pathways and the promoter sequences that mediate this regulation. Primary culture rabbit corneal epithelial cells were treated with various cytokines alone or in different combinations and MMP‐9 induction was assessed by gel zymography. Pharmacological inhibitors were used to determine the intracellular signaling pathways induced by the cytokines tested and deletion promoter constructs were created to determine the regions of the MMP‐9 promoter involved in the cytokine regulation, thereby assessing the exact transcription factors binding the MMP‐9 promoter. We found that two cytokine families, transforming growth factor β (TGF‐β) and interleukin 1 (IL‐1), act additively in an isoform non‐specific manner to induce MMP‐9 in this cell type. Our data suggest TGF‐β mediated MMP‐9 induction may be regulated by the NF‐κB, Smad3, and JNK pathways, whereas the IL‐1β mediated induction may be regulated by the NF‐κB and p38 pathways. Inhibition of the p38, NF‐κB, or JNK pathways significantly reduced, but did not abrogate, basal MMP‐9 levels. Inhibition of the ERK pathway did not have an effect on MMP‐9 mediated expression in either the treated or untreated co‐transfected cells. J. Cell. Physiol. 221: 402–411, 2009.Keywords
This publication has 71 references indexed in Scilit:
- TGF-β coordinately activates TAK1/MEK/AKT/NFkB and SMAD pathways to promote osteoclast survivalExperimental Cell Research, 2008
- TGF-β activates Erk MAP kinase signalling through direct phosphorylation of ShcAThe EMBO Journal, 2007
- Inhibition of Human Corneal Epithelial Production of Fibrotic Mediator TGF-β2 by Basement Membrane–Like Extracellular MatrixInvestigative Opthalmology & Visual Science, 2007
- TGF-β induces p65 acetylation to enhance bacteria-induced NF-κB activationThe EMBO Journal, 2007
- Smad-Sp1 complexes mediate TGF -induced early transcription of oncogenic Smad7 in pancreatic cancer cellsCarcinogenesis: Integrative Cancer Research, 2006
- Transcription Factors Pax6 and AP-2α Interact To Coordinate Corneal Epithelial Repair by Controlling Expression of Matrix Metalloproteinase Gelatinase BMolecular and Cellular Biology, 2004
- Regulation of MMP-9 Production by Human Corneal Epithelial CellsExperimental Eye Research, 2001
- AP-1 in cell proliferation and survivalOncogene, 2001
- Matrix metalloproteinase activity is enhanced during corneal wound repair in high glucose conditionCurrent Eye Research, 2000
- Differential roles for two gelatinolytic enzymes of the matrix metalloproteinase family in the remodelling corneaDevelopmental Biology, 1991