During wound healing and remodeling of the corneal stroma, biosynthesis and degradation of the extracellular matrix by keratocytes must be controlled spatially and temporally. Excess collagenase secretion results in corneal ulceration. Recent findings of collagenase and stromelysin induction by signal transduction through the fibronectin receptor (FnR) in synovial fibroblasts has led the applicant to examine the role of the FnR in the induction of keratocyte collagenase. The hypothesis is that the keratocyte FnR distinguishes between intact Fn and Fn fragments; the cellular response to the latter is activation of the collagenase pathway.
The aims are to determine: if keratocytes express collagenase when exposed to Fn, Fn fragments, or to antibody against the FnR; if the induced collagenase is secreted or stored; and which collagenases are induced and if they differ from those induced by cytochalasin B and the tumor promoter PMA. The long-term goal is to determine how the keratocyte and the extracellular matrix interact in normal and pathologic situations such as wound healing or keratoconus.
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| Masur, S K; Cheung, J K; Antohi, S (1993) Identification of integrins in cultured corneal fibroblasts and in isolated keratocytes. Invest Ophthalmol Vis Sci 34:2690-8 |
