Stress-Induced Hormones Cortisol and Epinephrine Impair Wound Epithelization

Stojadinović, Olivera; Gordon, Katherine; Lebrun, Elizabeth; Tomic‐Canic, Marjana

doi:10.1089/wound.2011.0320

Cited by 31 publications

(19 citation statements)

References 20 publications

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“…Using three immunologically diverse mouse models of inflammatory disease, irritant contact dermatitis (ICD), acute allergic contact dermatitis, and repeated hapten challenge in a model of chronic allergic contact dermatitis with features of AD, the investigators found that imposition of exogenous stress exerts potent antiinflammatory activity (reductions in IL-1a and IL-6), thus improving both barrier function and stratum corneum hydration, all of which is mediated by a rise in endogenous GCs (Figure 1b). This systemic GC protective effect, in contrast to the existing literature, suggests that the stress effects of increased endogenous GCs compromise permeability barrier homeostasis, stratum corneum adhesion, wound healing, and epidermal innate immunity in normal skin (Stojadinovic et al, 2012). Possibly, the differences in results lie in responses that originate from normal as opposed to inflamed skin.…”

mentioning

confidence: 61%

Stressing the Steroids in Skin: Paradox or Fine-Tuning?

Jozic

Stojadinović

Kirsner

et al. 2014

Journal of Investigative Dermatology

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The skin has recently been found to be an extra-adrenal site for glucocorticoid (GC) synthesis that likely acts to modulate local inflammation. Psychological, physiological, and physical stress, both acute and chronic, triggers immune-protective or -damaging responses, including increases in systemic GC levels, which, according to Lin et al. (this issue), may be beneficial in inflammatory skin disease. However, little is known about the interplay between local and systemic production of GCs and the effect of stress (local or systemic) in regulating tissue-specific GC synthesis, its impact on skin homeostasis, and its effect of skin disease.

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mentioning

confidence: 61%

Stressing the Steroids in Skin: Paradox or Fine-Tuning?

Jozic

Stojadinović

Kirsner

et al. 2014

Journal of Investigative Dermatology

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“…Thus, these cells are hyperproliferative and mitotically active at the edge of chronic wounds. But they fail to migrate and create a hyperkeratotic tissue at the edge of the wound (Stojadinovic et al, 2012;Martin and Nunan, 2015).…”

Section: Keratinocytesmentioning

confidence: 99%

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Casado-Díaz

Quesada‐Gómez

Dorado

2020

Front. Bioeng. Biotechnol.

232

183

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The cells secrete extracellular vesicles (EV) that may have an endosomal origin, or from evaginations of the plasma membrane. The former are usually called exosomes, with sizes ranging from 50 to 100 nm. These EV contain a lipid bilayer associated to membrane proteins. Molecules such as nucleic acids (DNA, mRNA, miRNA, lncRNA, etc.) and proteins may be stored inside. The EV composition depends on the producer cell type and its physiological conditions. Through them, the cells modify their microenvironment and the behavior of neighboring cells. That is accomplished by transferring factors that modulate different metabolic and signaling pathways. Due to their properties, EV can be applied as a diagnostic and therapeutic tool in medicine. The mesenchymal stromal cells (MSC) have immunomodulatory properties and a high regenerative capacity. These features are linked to their paracrine activity and EV secretion. Therefore, research on exosomes produced by MSC has been intensified for use in cell-free regenerative medicine. In this area, the use of EV for the treatment of chronic skin ulcers (CSU) has been proposed. Such sores occur when normal healing does not resolve properly. That is usually due to excessive prolongation of the inflammatory phase. These ulcers are associated with aging and diseases, such as diabetes, so their prevalence is increasing with the one of such latter disease, mainly in developed countries. This has very important socio-economic repercussions. In this review, we show that the application of MSC-derived EV for the treatment of CSU has positive effects, including accelerating healing and decreasing scar formation. This is because the EV have immunosuppressive and immunomodulatory properties. Likewise, they have the ability to activate the angiogenesis, proliferation, migration, and differentiation of the main cell types involved in skin regeneration. They include endothelial cells, fibroblasts, and keratinocytes. Most of the studies carried out so far are preclinical. Therefore, there is a need to advance more in the knowledge about the conditions of production, isolation, and action mechanisms of EV. Interestingly, their potential application in the treatment of CSU opens the door for the design of new highly effective therapeutic strategies.

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“…The physiologic stress response involves two pathways—the hypothalamic–pituitary adrenal axis, which releases glucocorticoids, such as cortisol, and the sympatho‐adrenomedullary axis, which releases catecholamines . As an example, glucocorticoids and catecholamines bind to their respective keratinocyte receptors and inhibit epithelialization . Likewise, antagonizing these receptors speeds healing; for example, patients suffering from burn wounds taking the beta‐adrenergic antagonist, propranolol had shorter healing times of their burn wounds and a shorter time‐to‐skin‐graft healing …”

mentioning

confidence: 99%

Statins may be associated with six‐week diabetic foot ulcer healing

Fox

Baquerizo-Nole

MacQuhae

et al. 2016

Wound Repair Regeneration

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Diabetic foot ulcers (DFUs) affect 1.5 million Americans annually, of which only a minority heal with standard care, and they commonly lead to amputation. To improve care, investigations are underway to better understand DFU pathogenesis and develop more effective therapies. Some currently used medications may improve healing. One small, randomized clinical trial found statins improve DFU healing. In this secondary analysis of a large multisite prospective observational cohort of 139 patients with DFUs receiving standard care, we investigated whether there was an association between 6-week DFU wound size reduction and use of a variety of medications including alpha-blockers, beta-blockers, angiotensin converting enzyme inhibitors (ACEi) and statins. We found no significant (p < 0.05) association between six-week wound reduction and use of any of the evaluated drugs; however, statins did trend toward an association (p = 0.057). This suggests a potential benefit of statins on DFU healing, and larger, targeted studies are warranted.

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Stress-Induced Hormones Cortisol and Epinephrine Impair Wound Epithelization

Cited by 31 publications

References 20 publications

Stressing the Steroids in Skin: Paradox or Fine-Tuning?

Stressing the Steroids in Skin: Paradox or Fine-Tuning?

Extracellular Vesicles Derived From Mesenchymal Stem Cells (MSC) in Regenerative Medicine: Applications in Skin Wound Healing

Statins may be associated with six‐week diabetic foot ulcer healing

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