Keratinocyte Migration and the Extracellular Matrix

Donaldson, Donald J.; Mahan, James T.

doi:10.1111/1523-1747.ep12560762

Cited by 58 publications

(21 citation statements)

References 96 publications

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“…The phenomenon of migration is influenced by the nature of the surrounding extracellular matrix and the protein composition of the wound environment (Donaldson, Mahan, 1988;Bernstein et al, 1996). Therefore, the coagulant action of the proanthocyanidins present in the barbatimão ointment may interfere with migration of the keratinocytes.…”

Section: Resultsmentioning

confidence: 99%

Wound-healing evaluation of ointment from Stryphnodendron adstringens (barbatimão) in rat skin

Hernandes

Pereira

Palazzo

et al. 2010

Braz. J. Pharm. Sci.

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This study evaluated the cicatrizant effect of an ointment containing 1% of the ethyl-acetate fraction extracted from the stem bark of "barbatimão" (Stryphnodendron adstringens), in wounds made in the skin of rats, after 4, 7 and 10 days of treatment. Control wounds were treated with a base ointment without extract. The proliferation of keratinocytes in the area of reepithelialization was evaluated by counting the number of epithelial cells that were blocked in metaphase by vincristine sulfate. The length of the reepithelialized margin and the contraction of the wound were measured. Topical application of the "barbatimão" ointment stimulated proliferation of the keratinocytes, but had no effect on the length of the epithelium or on the contraction of the wounds. Uniterms:Stryphnodendron adstringens/pharmacognosy. Stryphnodendron adstringens/ cicatrizant effect. "Barbatimão"/pharmacognosy. Wound/healing/experimental study. Reepithelialization.Neste estudo, avaliou-se a atividade cicatrizante de uma pomada contendo uma fração acetato de etila 1% obtida de cascas de "barbatimão" (Stryphnodendron adstringens) em feridas excisionais na pele de ratos após 4, 7 e 10 dias de tratamento. Feridas controle foram tratadas com pomada base, sem extrato. A proliferação dos queratinócitos na área reepitelizada foi avaliada através da contagem do número de queratinócitos bloqueados em metáfase, pelo sulfato de vincristina. O comprimento da margem reepitelizada e a contração das feridas foram mensurados. As feridas tratadas com barbatimão apresentaram um maior número de mitoses do que aquelas tratadas com a pomada base, em todos os tempos avaliados. A aplicação tópica da pomada de "barbatimão" estimulou a proliferação epitelial contudo não teve efeito sobre a migração dos queratinócitos ou sobre a contração das feridas. Unitermos:Stryphnodendron adstringens/farmacognosia. Stryphnodendron adstringens/efeito cicatrizante. "Barbatimão"/farmacognosia. Feridas/cicatrização/estudo experimental. Reepitelização. INTRODUCTIONIn cutaneous lesions, tannins bind to the proteins of the injured tissues, precipitating them (Fernandez et al., 2002) and creating a protective layer (Neto et al., 1996). This layer isolates the wound site from the environment, reducing the permeability and exudation of the wound (Brown, Dattner, 1998;Bedi, Shenefelt, 2002) and promoting tissue repair. Tannins also exhibit vasoconstrictor and anti-inflammatory properties (Mota et al., 1985;Kapu et al., 2001) and stimulate the growth of epidermis, aiding reepithelialization (Palermo et al., 2002;. Reepithelialization involves the proliferation and migration of cells from the edges of the wound, and is regulated by mechanisms involving genes, growth factors, integrins, extracellular matrices (ECM) and metalloproteinases (MMPs) (Santoro, Gaudino, 2005).Stryphnodendron Martius, Leguminosae, popularly known as "barbatimão", is a Brazilian savannah tree. Extracts of the stem bark from species of Stryphnodendron have several medically useful properties, such as antiinflamma...

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Section: Resultsmentioning

confidence: 99%

Wound-healing evaluation of ointment from Stryphnodendron adstringens (barbatimão) in rat skin

Hernandes

Pereira

Palazzo

et al. 2010

Braz. J. Pharm. Sci.

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“…In wounded skin, KCs are thought to migrate both individually and as a cellular sheet (Donaldson and Mahan, 1988). In the AGKOS assay, which uses standard plastic dishes, KCs move over the extracellular matrix proteins (i.e.…”

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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“…These cellular movements require changes in cell-cell and cell-matrix adhesion and massive actin cytoskeletal reorganization. Several additional critical physiological processes in skin, such as wound healing and hair follicle (HF) cycling (1)(2)(3), also require reorganization of the actin cytoskeleton. Aberrant cytoskeletal regulation is associated with a variety of human disorders of the skin (4,5).…”

Section: Introductionmentioning

confidence: 99%

Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice

Lyubimova

Garber²,

Upadhyay³

et al. 2010

J. Clin. Invest.

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Keratinocyte Migration and the Extracellular Matrix

Cited by 58 publications

References 96 publications

Wound-healing evaluation of ointment from Stryphnodendron adstringens (barbatimão) in rat skin

Wound-healing evaluation of ointment from Stryphnodendron adstringens (barbatimão) in rat skin

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

Neural Wiskott-Aldrich syndrome protein modulates Wnt signaling and is required for hair follicle cycling in mice

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