Andalusian Center of Molecular Biology and Regenerative Medicine CABIMER, Junta de Andalucia-University of Pablo de Olavide-University of Seville-CSIC, Seville, Spain.
Centro de Investigacion Biomedica en Red de Diabetes y Enfermedades Metabolicas Asociadas (CIBERDEM), Madrid, Spain.
Int J Biol Sci. 2023 Aug 6;19(13):4157-4165. doi: 10.7150/ijbs.86492. eCollection 2023.
Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from expression and activation is Prostaglandin E (PGE), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the -PGE signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.
前列腺素是参与生理过程的脂类介质，如血管的收缩或扩张，但也参与包括炎症、疼痛和发热在内的病理生理过程。它们由机体几乎所有细胞类型通过激活前列腺素内过氧化物合酶/环氧化酶来产生。诱导型前列腺素内过氧化物合酶 2/环氧化酶 2（PTGS2/COX2）在与炎症信号相关的病理中起着重要作用。表达和激活的主要产物是前列腺素 E（PGE），它促进了广泛的组织特异性效应，取决于环境输入。PGE 的主要来源之一是浸润性炎症细胞 - 在受损组织中这种分子的产生急剧增加。免疫浸润是 1 型糖尿病的标志，这是一种多因素疾病，导致自身免疫介导的胰腺β细胞破坏。已经报道了对于在致糖尿病条件下的胰岛细胞中 -PGE 信号级联的有争议的影响，将 PGE 分配为炎症的原因和结果。在此，我们以组织特异性的方式综述了该分子途径的主要作用，特别强调了β细胞质量的保护/破坏及其在 T1DM 的预防或发展中的潜在作用。我们还讨论了针对该途径的未来治疗策略。
