Experimental dermatology
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Current understanding of the complex process of wound repair is based on decades of study. Integral to this understanding has been the use of in vitro and in vivo models to uncover the key molecular players. ⋯ Here, we discuss the benefits and limitations of current animal-based models and highlight the urgent need for improved predictive preclinical models for wound healing research. We conclude by suggesting directions where more robust models of chronic wound pathologies may arise, expediting the development of novel therapies.
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Experimental dermatology · Mar 2012
Anti pruritic effects of topical crotamiton, capsaicin, and a corticosteroid on pruritogen-induced scratching behavior.
Itch accompanies various skin diseases. As a number of mediators other than histamine can be involved in the itch sensation, H1 receptor antagonists are not necessarily effective in treating itch. External application of antipruritic drugs is occasionally used as an alternative therapy for pruritic skin conditions, such as pruritus on primary non-diseased, non-inflamed skin. ⋯ Therapeutic effects of capsaicin on substance P-induced pruritus did not seem to be mediated by desensitization of the TRPV1 (+) C fibers and/or by altered responsiveness of the mast cells. In addition, the antipruritic effects of crotamiton and corticosteroid appear to be, at least partly, associated with a TRPV1-independent pathway. This study examined the itch responses to pruritogens and demonstrated the mode of action of the externally applied antipruritic drugs.
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Experimental dermatology · Feb 2012
Involvement of RAGE, MAPK and NF-κB pathways in AGEs-induced MMP-9 activation in HaCaT keratinocytes.
Advanced glycation end products (AGEs) exert divergent effects on the pathogenesis of diabetes complications. Excessive expression of matrix metalloproteinases-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. However, the effect of AGEs on MMP-9 induction in skin cells and the exact molecular mechanisms involved are still poorly understood. ⋯ We also observed the involvement of NF-κB in AGE-BSA-induced MMP-9 activation, which was not blocked by U0126 and SB203580. These results suggest that AGEs may play an important role in the impairment of diabetic wound healing by upregulating MMP-9 expression in keratinocytes via the RAGE, ERK1/2 and p38 MAPK pathways; activation of NF-κB is also involved in this process. These pathways may represent potential targets for drug interventions to improve diabetic wound healing, a process in which MMP-9 plays a critical role.
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Experimental dermatology · Dec 2011
Distinct SPINK5 and IL-31 polymorphisms are associated with atopic eczema and non-atopic hand dermatitis in Taiwanese nursing population.
The term 'hand dermatitis' describes inflammatory skin condition localized to the hands. Nurses working at hospital settings are prone to develop hand dermatitis. The current study aimed to evaluate whether certain genetic polymorphisms were associated with the development of atopic eczema or non-atopic hand dermatitis in Taiwanese population. ⋯ Our results showed that rs2303070 T allele of SPINK5 (assuming recessive model; OR=3.58, 95% CI 1.63-7.84; P=0.0014) and rs7977932 G allele of IL-31 (assuming recessive model; OR=18.25, 95% CI =3.27-101.94; P=0.0009) were associated with increased risks of developing atopic eczema, while rs6892205 G allele of SPINK5 (assuming dominant model; OR=3.79, 95% CI 1.55-9.28; P=0.0036) was associated with the development of non-atopic hand dermatitis. In summary, our results showed that distinct SPINK5 and IL-31 gene variants were associated with the development of atopic eczema and non-atopic hand dermatitis. The barrier function, particularly those regulated by SPINK5, may play an important role in the development of both atopic eczema and non-atopic hand dermatitis.
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Experimental dermatology · Dec 2011
Depigmenting action of platycodin D depends on the cAMP/Rho-dependent signalling pathway.
The overproduction and accumulation of melanin in the skin could lead to a pigmentary disorders, such as melasma, freckle, postinflammatory melanoderma and solar lentigo. Therefore, this study was conducted to investigate the effects of platycodin D (PD) on melanogenesis and its action mechanisms. In this study, we found that PD significantly inhibited melanin synthesis at low concentrations. ⋯ Moreover, a Rho inhibitor (C3 exoenzyme) and a Rho kinase inhibitor (Y27632) attenuated the dendrite retraction induced by PD. Taken together, these findings indicate that PD inhibits melanogenesis by inhibiting the cAMP-protein kinase A pathway and also suppresses melanocyte dendricity through activation of the Rho signal that is mediated by PD-induced reduction in cAMP production. Therefore, these results suggest that PD exerts its inhibitory effects on melanogenesis and melanocyte dendricity via suppression of cAMP signalling and may be introduced as an inhibitor of hyperpigmentation caused by UV irradiation or pigmented skin disorders.