Fibroblasts in Wound Healing: Transformation, Integrin expression, Motility and Proliferation differences in Syndecan‐1 deficient Mice

Activated fibroblasts are important in wound healing. Syndecan‐1 (sdc‐1), a heparan sulfate integral membrane proteoglycan, is upregulated in epithelial and mesenchymal cells in response to injury. Sdc‐1 deficient mice show delayed corneal and skin wound healing. We studied whether loss of sdc‐1 in primary dermal fibroblasts altered the proliferation, motility, integrin expression and conversion of fibroblasts to myofibroblasts using primary sdc‐1 null (−/−) and wild type (+/+) fibroblast cultures. Results show that −/− fibroblasts start becoming αSMA positive myofibroblasts at earlier time points than do the +/+ fibroblasts. In timelapse migration studies, the velocity of −/− fibroblasts is significantly higher than that of the +/+ cells from day 2 to 5. The mitotic index (MI) of +/+ fibroblasts is higher at day 3 and decreases by day 5 when compared to −/−. +/+ and −/− day 3 fibroblasts were treated with TGF‐β at 10 ng/ml. Cell motility, MI index , pattern of αSMA, αv, α5 and β1 expression were studied 48 hours later. TGF‐β decreases fibroblast to myofibroblast conversion in −/− cells. The velocity of both −/− and +/+ fibroblasts increases after treatment with TGF‐β. The MI decreases for both +/+ and −/− after treatment but the decrease being more pronounced for +/+ cells. In conclusion, TGFβ treatment acts to minimize differences between the +/+ and the −/− fibroblasts. Research support from R01EY08512‐17 and R01EY13559‐05