Differences in Healing of Skin Wounds Caused by Burn and Freeze Injuries

Li, A K; Ehrlich, H. Paul; Trelstad, Robert L.; Koroly, Mary Jo; Schattenkerk, M. Eeftinck; Malt, Ronald A.

doi:10.1097/00000658-198002000-00019

Cited by 79 publications

(60 citation statements)

References 6 publications

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“…Healed skin at these sites is rough and wrinkled. 49 Studies to determine whether collagen contraction could play a similar role in photoaged skin are in progress.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Varani

Spearman

Perone

et al. 2001

The American Journal of Pathology

290

208

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Type I and type III procollagen are reduced in photodamaged human skin. This reduction could result from increased degradation by metalloproteinases and/or from reduced procollagen synthesis. In the present study, we investigated type I procollagen production in photodamaged and sun-protected human skin. Skin samples from severely sun-damaged forearm skin and matched sun-protected hip skin from the same individuals were assessed for type I procollagen gene expression by in situ hybridization and for type I procollagen protein by immunostaining. Both mRNA and protein were reduced (ϳ65 and 57%, respectively) in photodamaged forearm skin compared to sun-protected hip skin. We next investigated whether reduced type I procollagen production was because of inherently reduced capacity of skin fibroblasts in severely photodamaged forearm skin to synthesize procollagen, or whether contextual influences within photodamaged skin act to down-regulate type I procollagen synthesis. For these studies, fibroblasts from photodamaged skin and matched sunprotected skin were established in culture. Equivalent numbers of fibroblasts were isolated from the two skin sites. Fibroblasts from the two sites had similar growth capacities and produced virtually identical amounts of type I procollagen protein. These findings indicate that the lack of type I procollagen synthesis in sun-damaged skin is not because of irreversible damage to fibroblast collagen-synthetic capacity. It follows, therefore, that factors within the severely photodamaged skin may act in some manner to inhibit procollagen production by cells that are inherently capable of doing so. Interactions between fibroblasts and the collagenous extracellular matrix regulate type I procollagen synthesis. In sun-protected skin, collagen fibrils exist as a highly organized matrix. Fibroblasts are found within the matrix, in close apposition with collagen fibers. In photodamaged skin, collagen fibrils are shortened, thinned, and disorganized. The level of partially degraded collagen is ϳ3.6-fold greater in photodamaged skin than in sun-protected skin, and some fibroblasts are surrounded by debris. To model this situation, skin fibroblasts were cultured in vitro on intact collagen or on collagen that had been partially degraded by exposure to collagenolytic enzymes. Collagen that had been partially degraded by exposure to collagenolytic enzymes from either bacteria or human skin underwent contraction in the presence of dermal fibroblasts, whereas intact collagen did not. Fibroblasts cultured on collagen that had been exposed to either source of collagenolytic enzyme demonstrated reduced proliferative capacity (22 and 17% reduction on collagen degraded by bacterial collagenase or human skin collagenase, respectively) and synthesized less type I procollagen (36 and 88% reduction, respectively, on a per cell basis). Taken together, these findings indicate that 1) fibroblasts from photoaged and sun-protected skin are similar in their capacities for growth and type I procollagen productio...

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“…Healed skin at these sites is rough and wrinkled. 49 Studies to determine whether collagen contraction could play a similar role in photoaged skin are in progress.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Varani

Spearman

Perone

et al. 2001

The American Journal of Pathology

290

208

View full text Add to dashboard Cite

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“…PKC-δ has been reported to play a major role in initiating and sustaining cell migration (Andre et al, 1999;Keller et al, 2000;Kruger and Reddy, 2003;Li et al, 1980), and in tumorcell metastasis (Kiley et al, 1999). The signaling pathway involving both PKC-δ and RhoA has been implicated in mediating regulation of cell motility downstream of other types of cell surface receptors, such as the leukotriene D 4 , lysophosphatidic acid and bombesin receptors (Barry and Critchley, 1994;Massoumi et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes

Chernyavsky

Arredondo

Marubio

et al. 2004

Journal of Cell Science

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Nicotinergic agents can act as both chemokines and chemoattractants for cell migration. Epidermal keratinocytes both synthesize acetylcholine and use it as a paracrine and autocrine regulator of cell motility. To gain a mechanistic insight into nicotinergic control of keratinocyte motility, we determined types of nicotinic acetylcholine receptors and signaling pathways regulating keratinocyte chemokinesis and chemotaxis, using respective modifications of the agarose gel keratinocyte outgrowth assay. Random migration of keratinocytes was significantly (P<0.05) inhibited by hemicholinum-3, a metabolic inhibitor of acetylcholine synthesis, as well as by the α-conotoxins MII and AuIB, preferentially blocking α3-containing nicotinic acetylcholine receptors. The use of antisense oligonucleotides specific for nicotinic-acetylcholine-receptor subunits and knockout mice demonstrated pivotal role for the α3β2 channel in mediating acetylcholine-dependent chemokinesis. Signaling pathways downstream of α3β2 included activation of the protein-kinase-C isoform δ and RhoA-dependent events. The nicotinergic chemotaxis of keratinocytes was most pronounced towards the concentration gradient of choline, a potent agonist of α7 nicotinic acetylcholine receptor. The α7-preferring antagonist α-bungarotoxin significantly (P<0.05) diminished keratinocyte chemotaxis, further suggesting a central role for the α7 nicotinic acetylcholine receptor. This hypothesis was confirmed in experiments with anti-α7 antisense oligonucleotides and α7-knockout mice. The signaling pathway mediating α7-dependent keratinocyte chemotaxis included intracellular calcium, activation of calcium/calmodulin-dependent protein-kinase II, conventional isoforms of protein-kinase C, phosphatidylinositol-3-kinase and engagement of Rac/Cdc42. Redistribution of α7 immunoreactivity to the leading edge of keratinocytes upon exposure to a chemoattractant preceded crescent shape formation and directional migration. Application of high-resolution deconvolution microscopy demonstrated that, on the cell membrane of keratinocytes, the nicotinic acetylcholine receptor subunits localize with the integrin β1. The obtained results demonstrate for the first time that α3 and α7 nicotinic acetylcholine receptors regulate keratinocyte chemokinesis and chemotaxis, respectively, and identify signaling pathways mediating these functions, which has clinical implications for wound healing and control of cancer metastases.

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“…The result is that the extracellular matrix and scaffold structure of the nerves and vessels remain intact, allowing the affected axon/myelin sheath or vascular cells to regenerate and repair the injury site. In comparison, heat lesions have been found to not only destroy cells but also disrupt the structural matrix, resulting in a narrower therapeutic window [33][34][35]. A recent study [36] demonstrated that following a traumatic peripheral nerve injury, the regenerated myelin sheath was thinner and exhibited a decreased intermodal length.…”

Section: Safety Of Cryoneurolysismentioning

confidence: 99%

Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves

Ilfeld

Preciado

Trescot

2016

Expert Review of Medical Devices

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Introduction: Cryoneurolysis is the direct application of low temperatures to reversibly ablate peripheral nerves to provide pain relief. Recent development of a handheld cryoneurolysis device with small gauge probes and an integrated skin warmer broadens the clinical applications to include treatment of superficial nerves, further enabling treatments for pre-operative pain, post-surgical pain, chronic pain, and muscle movement disorders. Areas covered: Cryoneurolysis is the direct application of cold temperatures to a peripheral nerve, resulting in reversible ablation due to Wallerian degeneration and nerve regeneration. Use over the last 50 years attests to a very low incidence of complications and adverse effects. Cryoprobes have traditionally been applied through a surgical incision; but, recent technical advances allow percutaneous administration. A new hand-held device is now approved for use within the United States. Cryoneurolysis has been used to treat postoperative and chronic pain states as well as spasticity. Expert commentary: Changes in the US healthcare system such as a push for the reduction of opioid use and the incorporation of Diagnostic Related Group codes, as well as recent technological advances including a handheld unit that allows for treatment of superficial nerves while protecting the skin from damage, may contribute to the resurgence of cryoneurolysis for the treatment of peripheral nerves. ARTICLE HISTORY

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Differences in Healing of Skin Wounds Caused by Burn and Freeze Injuries

Cited by 79 publications

References 6 publications

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Inhibition of Type I Procollagen Synthesis by Damaged Collagen in Photoaged Skin and by Collagenase-Degraded Collagen in Vitro

Differential regulation of keratinocyte chemokinesis and chemotaxis through distinct nicotinic receptor subtypes

Novel cryoneurolysis device for the treatment of sensory and motor peripheral nerves

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