Abstract
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.
