Department of Pharmacological and Pharmaceutical Sciences, College of Pharmacy, University of Houston, Houston TX 77204, U.S.A.
Clin Sci (Lond). 2022 Oct 28;136(20):1467-1470. doi: 10.1042/CS20220396.
Podocyte injury due to either drug, toxin, infection, or metabolic abnormality is a great concern as it increases the risk of developing focal segmental glomerulosclerosis (FSGS) and proteinuric kidney diseases. The direct podocyte injury due to doxorubicin is associated with an increase in proinflammatory cytokines and induction of cathepsin L. The increased activity of cathepsin L in turn may degrade the glomerular slit diaphragm resulting in proteinuric kidney injury. The angiotensin-II type 2 receptor (AT2R) has earlier been reported to be associated with the preservation of slit diaphragm proteins and prevention of proteinuria. Recent in vivo findings by Zhang and colleagues further support the anti-proteinuric role of AT2R in preventing podocyte injury via down-regulating cytokines ccl2, and hence, cathepsin L, thereby, limiting the progression of FSGS.
由于药物、毒素、感染或代谢异常导致的足细胞损伤是一个令人关注的问题，因为它会增加局灶节段性肾小球硬化症 (FSGS) 和蛋白尿性肾脏疾病的风险。阿霉素引起的直接足细胞损伤与促炎细胞因子的增加和组织蛋白酶 L 的诱导有关。组织蛋白酶 L 的活性增加反过来可能会降解肾小球裂孔隔膜，导致蛋白尿性肾损伤。血管紧张素 II 型受体 (AT2R) 先前已被报道与裂孔隔膜蛋白的保存和蛋白尿的预防有关。Zhang 及其同事的最近体内研究结果进一步支持了 AT2R 通过下调细胞因子 ccl2 从而抑制组织蛋白酶 L 的表达，从而限制 FSGS 进展，发挥其抗蛋白尿作用。
