Pontrelli Paola, Oranger Annarita, Barozzino Mariagrazia, Conserva Francesca, Papale Massimo, Gesualdo Loreto
Division of Nephrology, Dialysis and Transplantation, Department of Emergency and Organ Transplantation, Aldo Moro University of Bari, Bari, Italy -
Division of Nephrology, Dialysis and Transplantation, Department of Emergency and Organ Transplantation, Aldo Moro University of Bari, Bari, Italy.
Minerva Med. 2018 Feb;109(1):53-67. doi: 10.23736/S0026-4806.17.05419-2. Epub 2017 Oct 3.
Diabetic nephropathy (DN) is a chronic complication of type 2 diabetes and is the most frequent form of chronic kidney disease that can lead to end-stage renal disease. Different pathways, involved in oxidative stress, inflammation, fibrosis and cell death, are responsible for the pathogenesis of DN and regulate the progression of the disease. Ubiquitination is a fundamental pathway in intracellular signaling whose role is emerging in the regulation of molecular processes responsible for several human diseases. Among the conventional ubiquitination pathway, leading to proteasomal degradation of proteins, also non-conventional ubiquitination plays an important role in the regulation of intracellular signaling. Several proteasome inhibitors have been developed and tested both in humans and in animal models and show potential as promising therapeutic approaches. In this review, we focused our attention on the role of ubiquitination pathway in the principal processes involved in the pathogenesis and progression of DN.
糖尿病肾病(DN)是2型糖尿病的一种慢性并发症,是慢性肾脏病最常见的形式,可导致终末期肾病。参与氧化应激、炎症、纤维化和细胞死亡的不同途径是DN发病机制的原因,并调节疾病的进展。泛素化是细胞内信号传导的基本途径,其作用在负责多种人类疾病的分子过程调控中逐渐显现。在导致蛋白质经蛋白酶体降解的传统泛素化途径中,非传统泛素化在细胞内信号传导调控中也发挥着重要作用。几种蛋白酶体抑制剂已在人体和动物模型中开发并进行了测试,显示出作为有前景的治疗方法的潜力。在本综述中,我们重点关注泛素化途径在DN发病机制和进展所涉及的主要过程中的作用。