Gómez-Jaramillo Laura, Cano-Cano Fátima, Campos-Caro Antonio, Álcala Martín, Álvarez-Gallego Fabiola, Arroba Ana I, Aguilar-Diosdado Manuel
Unidad de Investigación, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), Cádiz, Spain; Departamento de Endocrinología y Nutrición, Hospital Universitario Puerta del Mar, Universidad de Cádiz, Cádiz, Spain.
Unidad de Investigación, Instituto de Investigación e Innovación en Ciencias Biomédicas de la Provincia de Cádiz (INiBICA), Cádiz, Spain; Área de Genética, Departamento de Biomedicina, Biotecnología y Salud Pública, Universidad de Cádiz, Cádiz, Spain.
Life Sci. 2022 Jul 1;300:120575. doi: 10.1016/j.lfs.2022.120575. Epub 2022 Apr 25.
Inflammatory processes play a central role in the pathogenesis of diabetic nephropathy (DN) in the early stages of the disease. In vitro approach using cell lines help to understand the mechanisms involves and allow the molecular and biochemical processes. Adult kidney (AK) explants remain an essential instrument for advancing our understanding of the molecular and cellular regulation of signalling pathways from an organotipic view with physiological system interaction integrated. AK explants from T1DM animal model (BB rat) are obtained by slicing central kidney area preserving the organ's cytoarchitecture and reproduce the classical events detected during the DN in an in vivo model such as inflammation, epithelial-mesenchymal transition (EMT) processes by the modulation of a-SMA and e-Cadherin among others which have been determined by qRT-PCR, western-blot and immunohistochemistry. In this regard, AK explants reproduce the signalling pathways involve in DN progression (proinflammatory NFkB and inflammasome complex). This work demonstrates AK explants is a physiological experimental approach for studying the development and progression of DN. Furthermore, the inflammatory processes in AK explants under a diabetic environment and/or BB rats could be modulated by potential treatments for DN.
炎症过程在糖尿病肾病（DN）发病机制的早期阶段起着核心作用。使用细胞系的体外方法有助于理解其中涉及的机制，并揭示分子和生化过程。成年肾脏（AK）外植体仍然是从器官层面观点以及整合生理系统相互作用来推进我们对信号通路分子和细胞调节理解的重要工具。来自1型糖尿病动物模型（BB大鼠）的AK外植体是通过切割肾脏中央区域获得的，保留了器官的细胞结构，并在体内模型中重现了DN过程中检测到的经典事件，如炎症、上皮-间质转化（EMT）过程，这些过程通过qRT-PCR、蛋白质免疫印迹和免疫组织化学等方法，由α-平滑肌肌动蛋白（α-SMA）和E-钙黏蛋白（E-Cadherin）等的调节得以确定。在这方面，AK外植体重现了DN进展过程中涉及的信号通路（促炎核因子κB（NFκB）和炎性小体复合物）。这项工作表明AK外植体是研究DN发生发展的一种生理学实验方法。此外，糖尿病环境下和/或BB大鼠的AK外植体中的炎症过程可通过DN的潜在治疗方法进行调节。
