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Constitutive collagenase‐1 synthesis through MAPK pathways is mediated, in part, by endogenous IL‐1α during fibrotic repair in corneal stroma
Author(s) -
Jung JaeChang,
Huh ManIl,
Fini M. Elizabeth
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21309
Subject(s) - collagenase , mapk/erk pathway , microbiology and biotechnology , interstitial collagenase , signal transduction , extracellular matrix , kinase , chemistry , fibroblast , protein kinase a , biology , biochemistry , enzyme , in vitro
Collagenase‐1 is a protease expressed by active fibroblasts that is involved in remodeling of the extracellular matrix (ECM). In this study, we characterize the intracellular signaling mechanism of collagenase‐1 production by IL‐1α in subcultured normal fibroblasts (NF) from uninjured normal corneas, compared to that in repair wound fibroblasts (WF). In NF, collagenase‐1 was induced specifically after the exogenous addition of IL‐1α via activation of ERK and p38MAPK. Collagenase‐1 expression was strongly suppressed upon treatment with either a MEK or p38MAPK inhibitor. In contrast, repair WF constitutively synthesized both IL‐1α and collagenase‐1. Combined treatment with both mitogen‐activated protein kinase (MAPK) inhibitors dramatically reduced collagenase‐1 synthesis, while individual MEK1 or p38 inhibitors weakly modulated the collagenase‐1 level. The results indicate that both pathways are crucial in the regulation of collagenase‐1 synthesis. Furthermore, an IL‐1α receptor antagonist (IL‐1ra) could not abolish constitutive collagenase‐1 synthesis, even at high doses, suggesting that other cytokines/factors are additionally involved in this process. We propose that induction of collagenase‐1 by IL‐1α in both WF and NF depends on a unique combination of cell type‐specific signaling pathways. J. Cell. Biochem. 102: 453–462, 2007. © 2007 Wiley‐Liss, Inc.