Department of Medical Sciences, University of Turin, Turin, Italy.
Clin Sci (Lond). 2022 Apr 14;136(7):493-520. doi: 10.1042/CS20210625.
Albuminuria is the hallmark of both primary and secondary proteinuric glomerulopathies, including focal segmental glomerulosclerosis (FSGS), obesity-related nephropathy, and diabetic nephropathy (DN). Moreover, albuminuria is an important feature of all chronic kidney diseases (CKDs). Podocytes play a key role in maintaining the permselectivity of the glomerular filtration barrier (GFB) and injury of the podocyte, leading to foot process (FP) effacement and podocyte loss, the unifying underlying mechanism of proteinuric glomerulopathies. The metabolic insult of hyperglycemia is of paramount importance in the pathogenesis of DN, while insults leading to podocyte damage are poorly defined in other proteinuric glomerulopathies. However, shared mechanisms of podocyte damage have been identified. Herein, we will review the role of haemodynamic and oxidative stress, inflammation, lipotoxicity, endocannabinoid (EC) hypertone, and both mitochondrial and autophagic dysfunction in the pathogenesis of the podocyte damage, focussing particularly on their role in the pathogenesis of DN. Gaining a better insight into the mechanisms of podocyte injury may provide novel targets for treatment. Moreover, novel strategies for boosting podocyte repair may open the way to podocyte regenerative medicine.
蛋白尿是原发性和继发性蛋白尿性肾小球疾病的标志，包括局灶节段性肾小球硬化症（FSGS）、肥胖相关性肾病和糖尿病肾病（DN）。此外，蛋白尿是所有慢性肾脏病（CKD）的一个重要特征。足细胞在维持肾小球滤过屏障（GFB）的选择性方面起着关键作用，足细胞损伤导致足突融合和足细胞丢失，这是蛋白尿性肾小球疾病的统一潜在机制。高血糖引起的代谢损伤在 DN 的发病机制中至关重要，而导致足细胞损伤的损伤因素在其他蛋白尿性肾小球疾病中尚未明确。然而，已经确定了足细胞损伤的共同机制。在此，我们将综述血流动力学和氧化应激、炎症、脂毒性、内源性大麻素（EC）高张力以及线粒体和自噬功能障碍在足细胞损伤发病机制中的作用，特别关注它们在 DN 发病机制中的作用。深入了解足细胞损伤的机制可能为治疗提供新的靶点。此外，促进足细胞修复的新策略可能为足细胞再生医学开辟道路。
