Centre de Recherche en Organogénèse Expérimentale de l'Université Laval/LOEX, Axe Médecine Régénératrice, Centre de Recherche du CHU de Québec-Université Laval, Québec, QC G1J 1Z4, Canada.
Faculté de Pharmacie, Université Laval, Québec, QC G1V 0A6, Canada.
Int J Mol Sci. 2020 Jul 23;21(15):5215. doi: 10.3390/ijms21155215.
Pathological and healthy skin models were reconstructed using similar culture conditions according to well-known tissue engineering protocols. For both models, cyclic nucleotide enhancers were used as additives to promote keratinocytes' proliferation. Cholera toxin (CT) and isoproterenol (ISO), a beta-adrenergic agonist, are the most common cAMP stimulators recommended for cell culture. The aim of this study was to evaluate the impact of either CT or ISO on the pathological characteristics of the dermatosis while producing a psoriatic skin model. Healthy and psoriatic skin substitutes were produced according to the self-assembly method of tissue engineering, using culture media supplemented with either CT (10 M) or ISO (10 M). Psoriatic substitutes produced with CT exhibited a more pronounced psoriatic phenotype than those produced with ISO. Indeed, the psoriatic substitutes produced with CT had the thickest epidermis, as well as contained the most proliferating cells and the most altered expression of involucrin, filaggrin, and keratin 10. Of the four conditions under study, psoriatic substitutes produced with CT had the highest levels of cAMP and enhanced expression of adenylate cyclase 9. Taken together, these results suggest that high levels of cAMP are linked to a stronger psoriatic phenotype.
采用相似的培养条件，根据已知的组织工程方案，重建病理性和健康皮肤模型。对于这两种模型，均使用环核苷酸增强剂作为添加剂，以促进角质形成细胞的增殖。霍乱毒素（CT）和异丙肾上腺素（ISO），一种β-肾上腺素能激动剂，是推荐用于细胞培养的最常见的 cAMP 刺激剂。本研究的目的是评估 CT 或 ISO 对皮肤病的病理性特征的影响，同时产生银屑病皮肤模型。采用组织工程的自组装方法，用补充有 CT（10μM）或 ISO（10μM）的培养基来生产健康和银屑病皮肤替代物。用 CT 产生的银屑病替代物表现出比用 ISO 产生的更明显的银屑病表型。事实上，用 CT 产生的银屑病替代物具有最厚的表皮，以及包含最多增殖细胞和最改变的角蛋白 10 的表达。在研究的四种条件中，用 CT 产生的银屑病替代物具有最高水平的 cAMP 和增强的腺苷酸环化酶 9 的表达。总之，这些结果表明，高水平的 cAMP 与更强的银屑病表型有关。
