Chang Jingsheng, Yan Jiayi, Li Xueling, Liu Ni, Zheng Rong, Zhong Yifei
Department of Nephrology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
Front Med (Lausanne). 2021 Mar 30;8:661076. doi: 10.3389/fmed.2021.661076. eCollection 2021.
Increasing evidence supports a role of proximal tubular (PT) injury in the progression of diabetic kidney disease (DKD), in patients with or without proteinuria. Research on the mechanisms of the PT injury in DKD could help us to identify potential new biomarkers and drug targets for DKD. A high glucose transport state and mismatched local hypoxia in the PT of diabetes patients may be the initiating factors causing PT injury. Other mechanism such as mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, ER stress, and deficiency of autophagy interact with each other leading to more PT injury by forming a vicious circle. PT injury eventually leads to the development of tubulointerstitial inflammation and fibrosis in DKD. Many downstream signaling pathways have been demonstrated to mediate these diseased processes. This review focuses mostly on the novel mechanisms of proximal renal tubular injury in DKD and we believe such review could help us to better understand the pathogenesis of DKD and identify potential new therapies for this disease.
越来越多的证据支持近端肾小管（PT）损伤在糖尿病肾病（DKD）进展中所起的作用，无论患者有无蛋白尿。对DKD中PT损伤机制的研究有助于我们识别DKD潜在的新生物标志物和药物靶点。糖尿病患者PT中高葡萄糖转运状态和局部缺氧不匹配可能是导致PT损伤的起始因素。其他机制，如线粒体功能障碍、活性氧（ROS）过度产生、内质网应激和自噬缺陷，相互作用，通过形成恶性循环导致更多的PT损伤。PT损伤最终导致DKD中肾小管间质炎症和纤维化的发展。许多下游信号通路已被证明介导这些疾病过程。本综述主要关注DKD中近端肾小管损伤的新机制，我们相信这样的综述有助于我们更好地理解DKD的发病机制，并确定该疾病潜在的新疗法。
