Garcia-Fernandez Nuria, Jacobs-Cachá Conxita, Mora-Gutiérrez José María, Vergara Ander, Orbe Josune, Soler María José
Nephrology Department, Clinica Universidad de Navarra, 31008 Pamplona, Spain.
Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Spain.
J Clin Med. 2020 Feb 8;9(2):472. doi: 10.3390/jcm9020472.
Around the world diabetic kidney disease (DKD) is the main cause of chronic kidney disease (CKD), which is characterized by mesangial expansion, glomerulosclerosis, tubular atrophy, and interstitial fibrosis. The hallmark of the pathogenesis of DKD is an increased extracellular matrix (ECM) accumulation causing thickening of the glomerular and tubular basement membranes, mesangial expansion, sclerosis, and tubulointerstitial fibrosis. The matrix metalloproteases (MMPs) family are composed of zinc-dependent enzymes involved in the degradation and hydrolysis of ECM components. Several MMPs are expressed in the kidney; nephron compartments, vasculature and connective tissue. Given their important role in DKD, several studies have been performed in patients with DKD proposing that the measurement of their activity in serum or in urine may become in the future markers of early DKD. Studies from diabetic nephropathy experimental models suggest that a balance between MMPs levels and their inhibitors is needed to maintain renal homeostasis. This review focuses in the importance of the MMPs within the kidney and their modifications at the circulation, kidney and urine in patients with DKD. We also cover the most important studies performed in experimental models of diabetes in terms of MMPs levels, renal expression and its down-regulation effect.
在全球范围内,糖尿病肾病(DKD)是慢性肾脏病(CKD)的主要病因,其特征为系膜扩张、肾小球硬化、肾小管萎缩和间质纤维化。DKD发病机制的标志是细胞外基质(ECM)积累增加,导致肾小球和肾小管基底膜增厚、系膜扩张、硬化以及肾小管间质纤维化。基质金属蛋白酶(MMPs)家族由参与ECM成分降解和水解的锌依赖性酶组成。几种MMPs在肾脏中表达,包括肾单位各部分、脉管系统和结缔组织。鉴于它们在DKD中的重要作用,针对DKD患者开展了多项研究,提出测定血清或尿液中它们的活性在未来可能成为早期DKD的标志物。糖尿病肾病实验模型的研究表明,需要MMPs水平与其抑制剂之间保持平衡以维持肾脏内环境稳定。本综述重点关注MMPs在肾脏中的重要性以及它们在DKD患者循环、肾脏和尿液中的变化。我们还涵盖了在糖尿病实验模型中就MMPs水平、肾脏表达及其下调作用所开展的最重要研究。