Dataset Information

Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing.

ABSTRACT: Hypoxia is a microenvironmental stress in wounded skin, where it supports wound healing by promoting cell motility. The mechanism of the hypoxia action remained speculative. Here, we provide evidence that hypoxia promotes human dermal fibroblast (HDF) migration by inducing secretion of heat shock protein-90alpha (hsp90alpha) into the extracellular environment through hypoxia-inducible factor-1alpha (HIF-1alpha). The secreted hsp90alpha in turn executes hypoxia's pro-motility effect. Expression of an activated HIF-1alpha mimicked, whereas expression of an inactive HIF-1alpha or suppression of endogenous HIF-1alpha blocked, hypoxia-induced hsp90alpha secretion and HDF migration. Interestingly, the hypoxia-HIF-1 pathway-induced hsp90alpha secretion required neither changes in the steady-state mRNA level nor in the promoter activity of hsp90alpha. Recombinant hsp90alpha fully duplicated the hypoxia effect on HDFs. Inhibition of extracellular hsp90alpha function completely blocked the hypoxia-HIF-1 pathway-stimulated HDF migration. More intriguingly, topical application of hsp90alpha accelerated wound healing in mice. This study has demonstrated a novel mechanism of hypoxia>HIF-1>hsp90alpha secretion>skin cell migration>wound healing, and identified extracellular hsp90alpha as a potential therapeutic agent for skin wounds.

SUBMITTER: Li W

PROVIDER: S-EPMC1817627 | biostudies-literature | 2007 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing.

Li Wei W Li Yong Y Guan Shengxi S Fan Jianhua J Cheng Chieh-Fang CF Bright Alexandra M AM Chinn Cindi C Chen Mei M Woodley David T DT

The EMBO journal 20070215 5

Hypoxia is a microenvironmental stress in wounded skin, where it supports wound healing by promoting cell motility. The mechanism of the hypoxia action remained speculative. Here, we provide evidence that hypoxia promotes human dermal fibroblast (HDF) migration by inducing secretion of heat shock protein-90alpha (hsp90alpha) into the extracellular environment through hypoxia-inducible factor-1alpha (HIF-1alpha). The secreted hsp90alpha in turn executes hypoxia's pro-motility effect. Expression o ...[more]

PMID: 17304217

Similar Datasets

Project description:Pressure ulcers (PUs) or sores are a secondary complication of diabetic neuropathy and traumatic spinal cord injury (SCI). PUs tend to occur in soft tissues located around bony prominences and may heal slowly or not at all. A common mechanism underlying impaired healing of PUs may be dysfunction of the local neurovascular system including deficiency of essential neuropeptides, such as substance P (SP). Previous studies indicate that disturbance in cutaneous sensory innervation leads to a defect in all stages of wound healing, as is the case after SCI. It is hypothesized that nerve fibers enhance wound healing by promoting initial inflammation via the releasing of neuropeptides such as SP. Therefore, we investigated whether exogenous SP improves skin wound healing using in vitro and in vivo models. For in vitro studies, the effects of SP on keratinocyte proliferation and wound closure after a scratch injury were studied under normoxia (pO2 ~21%) or hypoxia (pO2 ~1%) and in presence of normal serum (10% v/v) or low serum (1% v/v) concentrations. Hypoxia and low serum both significantly slowed cell proliferation and wound closure. Under combined low serum and hypoxia, used to mimic the nutrient- and oxygen-poor environment of chronic wounds, SP (10-7 M) significantly enhanced cell proliferation and wound closure rate. For in vivo studies, two full-thickness excisional wounds were created with a 5 mm biopsy punch on the dorsum on either side of the midline of 15-week-old C57BL/6J male and female mice. Immediately, wounds were treated topically with one dose of 0.5 μg SP or PBS vehicle. The data suggest a beneficial role in wound closure and reepithelization, and thus enhanced wound healing, in male and female mice. Taken together, exogenously applied neuropeptide SP enhanced wound healing via cell proliferation and migration in vitro and in vivo. Thus, exogenous SP may be a useful strategy to explore further for treating PUs in SCI and diabetic patients.

Dataset Information

Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing.

Publications

Extracellular heat shock protein-90alpha: linking hypoxia to skin cell motility and wound healing.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets