Schiffer Tomas A, Friederich-Persson Malou
Department of Medical Cell Biology, Uppsala UniversityUppsala, Sweden.
Department of Medical and Health Sciences, Linköping UniversityLinköping, Sweden.
Front Physiol. 2017 Apr 11;8:211. doi: 10.3389/fphys.2017.00211. eCollection 2017.
The underlying mechanisms in the development of diabetic nephropathy are currently unclear and likely consist of a series of dynamic events from the early to late stages of the disease. Diabetic nephropathy is currently without curative treatments and it is acknowledged that even the earliest clinical manifestation of nephropathy is preceded by an established morphological renal injury that is in turn preceded by functional and metabolic alterations. An early manifestation of the diabetic kidney is the development of kidney hypoxia that has been acknowledged as a common pathway to nephropathy. There have been reports of altered mitochondrial function in the diabetic kidney such as altered mitophagy, mitochondrial dynamics, uncoupling, and cellular signaling through hypoxia inducible factors and AMP-kinase. These factors are also likely to be intertwined in a complex manner. In this review, we discuss how these pathways are connected to mitochondrial production of reactive oxygen species (ROS) and how they may relate to the development of kidney hypoxia in diabetic nephropathy. From available literature, it is evident that early correction and/or prevention of mitochondrial dysfunction may be pivotal in the prevention and treatment of diabetic nephropathy.
目前，糖尿病肾病发展的潜在机制尚不清楚，可能由疾病早期到晚期的一系列动态事件组成。目前糖尿病肾病尚无治愈方法，而且人们认识到，即使是肾病最早的临床表现之前，就已经存在既定的形态学肾脏损伤，而这种损伤又先于功能和代谢改变。糖尿病肾脏的早期表现是肾脏缺氧的发生，这已被认为是肾病的共同途径。有报道称糖尿病肾脏中线粒体功能发生改变，如线粒体自噬、线粒体动力学、解偶联以及通过缺氧诱导因子和AMP激酶的细胞信号传导改变。这些因素也可能以复杂的方式相互交织。在本综述中，我们讨论了这些途径如何与线粒体活性氧（ROS）的产生相关联，以及它们如何与糖尿病肾病中肾脏缺氧的发展相关。从现有文献来看，早期纠正和/或预防线粒体功能障碍可能对糖尿病肾病的预防和治疗至关重要。
