The epidermal Integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors, while the expression of p75NTR is decreased in patients with chronic skin ulcers

Abstract

Background: More effective treatment strategies are needed for the chronic skin ulcers. Recently, it has been reported that clinical application of stem cells improve wound healing.

Objective: We aimed to determine the dynamic time-course movement of epidermal stem cell markers especially p75 neurotrophin receptor (p75NTR) and Integrin beta-1 in wound healing process. Furthermore, we also investigated the presence of these markers in human.

Methods: Epidermal Integrin beta-1(+) and p75NTR(+) cells were counted in wound healing process in mice. Both cells were also counted in human skin specimen obtained from chronic skin ulcers and healthy controls. Growth factor gene expression levels by purified mouse epidermal p75NTR(+) cells were also analyzed using real-time RT-PCR.

Results: Integrin beta-1(+) and p75NTR(+) cells were proliferated from 3 days after wounding. Reepithelization was completed 7 days after wounding, and the numbers of cells were returned to the baseline levels by 14 days after wounding. Integrin beta-1(+) cells were proliferated in the basal layer, and p75NTR(+) cells were proliferated in the upper layer of epidermis. In human skin, Integrin beta-1(+) and p75NTR(+) cells were 81%±12% and 36%±15% of the basal cells, respectively. In patients with chronic skin ulcers, the percentage of Integrin beta-1(+) cells in the epidermis was identical to healthy controls. Surprisingly, p75NTR(+) cells were significantly decreased in chronic skin ulcer patients (1.2%±2.6%; p<0.0005) compared to healthy controls. Purified mouse epidermal p75NTR(+) cells expressed higher transforming growth factor-beta2 and vascular endothelial growth factor-alpha transcripts and lower epidermal growth factor transcripts than p75NTR(-) cells.

Conclusion: These results suggest that Integrin beta-1(+) and p75NTR(+) cells play an important role in wound healing process, and that p75NTR may be a key molecule and a candidate for new therapeutic target besides preexisting molecules for chronic skin ulcer patients.

Keywords: CD271; CD29; Integrin beta-1; Stem cell; Wound healing; p75NTR.