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M. Stepp, R. A. Jurjus, Y. Liu, S. Pal-Ghosh, G. Tadvalkar; The Importance of Syndecan-1 (sdc-1) in Corneal Epithelial and Stromal Homeostasis. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2860.
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sdc-1 null mice are maintained on a Balb/c genetic background obtained by serial backcrosses (7) with Balb/cJ mice. Epidermal keratinocytes, dermal fibroblasts, and corneal fibroblasts were derived from sdc-1 null mice and wt Balb/c mice. Keratinocytes and dermal fibroblasts were used within 3-7 days after being placed in culture. Dermal and corneal fibroblasts were also used after 2-4 passages. Cells were used for time lapse studies and for various biochemical and functional analyses of protein expression and function.
Keratinocytes derived from sdc-1 null mice migrate slower than the wt keratinocytes primarily due to increased surface expression and function of α6β4 integrin. In contrast, both dermal and corneal fibroblasts show increased migration rates. Detailed studies of dermal fibroblasts show that the increased migration rate is the result of increased expression and function of β1 family integrins on the sdc-1 null cells. Both keratinocytes and fibroblasts show differences in TGFβ1 mediated signal transduction which is due in part of variations in αv-family integrin activity in the sdc-1 null cells. Whereas the migration differences in the sdc-1 null keratinocytes can be totally reverted using sdc-1 ectodomain peptides, the differences in migration of the sdc-1 null fibroblasts are only partially reverted.
The sdc-1 null mouse provides a unique opportunity to investigate corneal and skin responses to epidermal wounding using both in vivo and in vitro approaches. The reduced frequency of recurrent corneal erosions is due to enhanced integrin function in these mice. These studies are leading to an improved understanding of the roles of heparan sulfate proteoglycans in the pathological healing seen in corneas with erosions and stem cell deficiency.
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