Department of Biology, Faculty of Chemistry, National Autonomous University of Mexico (UNAM), Mexico City 04510, Mexico.
Department of Nephrology and Laboratory of Renal Pathophysiology, National Institute of Cardiology "Ignacio Chávez", Mexico City 14080, Mexico.
Biomolecules. 2019 Apr 8;9(4):141. doi: 10.3390/biom9040141.
Renal fibrosis is the common pathway for most forms of progressive renal disease. The Unilateral Ureteral Obstruction (UUO) model is used to cause renal fibrosis, where the primary feature of UUO is tubular injury as a result of obstructed urine flow. Furthermore, experimental UUO in rodents is believed to mimic human chronic obstructive nephropathy in an accelerated manner. Renal fibrosis is the common pathway for most forms of progressive renal disease. Removing the obstruction may not be sufficient to reverse fibrosis, so an accompanying treatment may be of benefit. In this review, we have done a revision on treatments shown to ameliorate fibrosis in the context of the UUO experimental model. The treatments inhibit the production of fibrotic and inflammatory proteins such as Transforming Growth Factor β1 (TGF-β₁), Tumor Necrosis Factor α (TNF-α), collagen and fibronectin, Heat Shock Protein 47 (HSP47), suppress the proliferation of fibroblasts, prevent epithelial-to-mesenchymal transition, reduce oxidative stress, inhibit the action of the Nuclear Factor κB (NF-κB), reduce the phosphorylation of mothers against decapentaplegic homolog (SMAD) family members 2 and 3 (Smad2/3) or Mitogen-Activated Protein Kinases (MAPKs), inhibit the activation of the renin-angiotensin system. Summaries of the UUO experimental methods and alterations observed in the UUO experiments are included.
肾脏纤维化是大多数进行性肾脏疾病的共同途径。单侧输尿管梗阻 (UUO) 模型用于引起肾脏纤维化,UUO 的主要特征是由于尿液流动受阻导致的肾小管损伤。此外,人们认为实验性 UUO 在啮齿动物中以加速的方式模拟人类慢性阻塞性肾病。肾脏纤维化是大多数进行性肾脏疾病的共同途径。去除梗阻可能不足以逆转纤维化,因此伴随的治疗可能有益。在这篇综述中,我们对在 UUO 实验模型背景下显示可改善纤维化的治疗方法进行了修订。这些治疗方法抑制纤维化和炎症蛋白的产生,如转化生长因子β₁ (TGF-β₁)、肿瘤坏死因子α (TNF-α)、胶原蛋白和纤维连接蛋白、热休克蛋白 47 (HSP47)、抑制成纤维细胞增殖、防止上皮细胞-间充质转化、减少氧化应激、抑制核因子 κB (NF-κB) 的作用、减少 Mothers Against Decapentaplegic Homolog (SMAD) 家族成员 2 和 3 (Smad2/3) 或丝裂原活化蛋白激酶 (MAPKs) 的磷酸化、抑制肾素-血管紧张素系统的激活。包括 UUO 实验方法的摘要和在 UUO 实验中观察到的改变。