Bone and Mineral Research Unit, Hospital Universitario Central de Asturias, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), Retic REDinREN-ISCIII, Universidad de Oviedo, 33011 Oviedo, Spain.
Pathology Department, Fundación Instituto de Investigaciones Sanitarias-Fundación Jiménez Díaz (IIS-FJD), Universidad Autónoma de Madrid (UAM), Retic REDinREN-ISCIII, 28040 Madrid, Spain.
Int J Mol Sci. 2021 Jan 2;22(1):408. doi: 10.3390/ijms22010408.
Fibrosis is a process characterized by an excessive accumulation of the extracellular matrix as a response to different types of tissue injuries, which leads to organ dysfunction. The process can be initiated by multiple and different stimuli and pathogenic factors which trigger the cascade of reparation converging in molecular signals responsible of initiating and driving fibrosis. Though fibrosis can play a defensive role, in several circumstances at a certain stage, it can progressively become an uncontrolled irreversible and self-maintained process, named pathological fibrosis. Several systems, molecules and responses involved in the pathogenesis of the pathological fibrosis of chronic kidney disease (CKD) will be discussed in this review, putting special attention on inflammation, renin-angiotensin system (RAS), parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), Klotho, microRNAs (miRs), and the vitamin D hormonal system. All of them are key factors of the core and regulatory pathways which drive fibrosis, having a great negative kidney and cardiac impact in CKD.
纤维化是一种以细胞外基质过度积累为特征的过程，是对各种类型的组织损伤的反应，可导致器官功能障碍。该过程可由多种不同的刺激物和致病因素引发，这些刺激物和致病因素触发修复级联反应，汇聚到负责启动和驱动纤维化的分子信号中。尽管纤维化可能具有防御作用，但在某些情况下，在某个阶段，它可能会逐渐变成一种无法控制的、不可逆转的自我维持过程，称为病理性纤维化。本文将讨论慢性肾脏病（CKD）病理性纤维化发病机制中涉及的几个系统、分子和反应，特别关注炎症、肾素-血管紧张素系统（RAS）、甲状旁腺激素（PTH）、成纤维细胞生长因子 23（FGF23）、Klotho、microRNAs（miRs）和维生素 D 激素系统。所有这些都是驱动纤维化的核心和调节途径的关键因素，对 CKD 的肾脏和心脏有很大的负面影响。
