Abstract
Inflammation, proliferation, and tissue remodeling are essential steps for wound healing. The hypoxic wound microenvironment promotes cell migration through a hypoxia—heat shock protein 90 alpha (Hsp90α)—low density lipoprotein receptor-related protein-1 (LRP-1) autocrine loop. To elucidate the role of this autocrine loop on burn wound healing, we investigated the expression profile of Hsp90α at the edge of burn wounds and found a transient increase in both mRNA and protein levels. Experiments performed with a human keratinocyte cell line—HaCaT also confirmed above results. 17-dimethylaminoethylamino-17demethoxygeldanamycin hydrochloride (17-DMAG), an Hsp90α inhibitor, was used to further evaluate the function of Hsp90α in wound healing. Consistently, topical application of Hsp90α in the early stage of deep second-degree burn wounds led to reduced inflammation and increased tissue granulation, with a concomitant reduction in the size of the wound at each time point tested (p<0.05). Consequently, epidermal cells at the wound margin progressed more rapidly causing an expedited healing process. In conclusion, these results provided a rationale for the therapeutic effect of Hsp90α on the burn wound management.
Highlights
There are three key phases in wound healing: inflammation, proliferation, and tissue remodeling [1]
Transforming growth factor-beta 3 (TGF-b3) is widely expressed in various tissues and can inhibit the wound-healing effects of platelet-derived growth factor (PDGF)-BB and vascular endothelial growth factor (VEGF), these cytokines alone are not sufficient to promote the migration of dermal fibroblasts (DFs) or human dermal microvascular endothelial cells (HDMECs) [11,12,13]
We evaluated the effect of heat shock protein 90 alpha (Hsp90a) on wound healing elicited by creating a scratch in heat-shocked immortalized human keratinocytes—HaCaT cells, an in vitro human skin equivalent model
Summary
There are three key phases in wound healing: inflammation, proliferation, and tissue remodeling [1]. Residual skin cells secret growth factors such as vascular endothelial growth factor (VEGF) [7] and platelet-derived growth factor (PDGF) [8]. These cytokines are widely accepted as the driving force behind wound healing [9]. Transforming growth factor-beta 3 (TGF-b3) is widely expressed in various tissues and can inhibit the wound-healing effects of PDGF-BB and VEGF, these cytokines alone are not sufficient to promote the migration of dermal fibroblasts (DFs) or human dermal microvascular endothelial cells (HDMECs) [11,12,13]. The mechanism driving the skin cell migration to the wound bed when TGF-b3 is abundantly expressed in the same tissue needs to be elucidated
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