The potential of recombinant human
prolidase (rhPEPD) to induce wound healing in an experimental model of IL-1β-induced
inflammation in human fibroblasts was studied. It was found that rhPEPD significantly increased cell proliferation and viability, as well as the expression of the
epidermal growth factor receptor (EGFR) and downstream signaling
proteins, such as phosphorylated PI3K, AKT, and mTOR, in the studied model. Moreover, rhPEPD upregulated the expression of the β1
integrin receptor and its downstream signaling
proteins, such as p-FAK, Grb2 and p-ERK 1/2. The inhibition of EGFR signaling by
gefitinib abolished rhPEPD-dependent functions in an experimental model of
inflammation. Subsequent studies showed that rhPEPD augmented
collagen biosynthesis in IL-1β-treated fibroblasts as well as in a wound healing model (
wound closure/scratch test). Although IL-1β treatment of fibroblasts increased cell migration, rhPEPD significantly enhanced this process. This effect was accompanied by an increase in the activity of MMP-2 and MMP-9, suggesting extracellular matrix (ECM) remodeling during the inflammatory process. The data suggest that rhPEPD may play an important role in EGFR-dependent cell growth in an experimental model of
inflammation in human fibroblasts, and this knowledge may be useful for further approaches to the treatment of abnormalities of wound healing and other
skin diseases.