Identification of cell division cycle protein 20 in various forms of acute and chronic kidney injury in mice

Tubular epithelial cell fate following exposure to various types of injurious stimuli can be decided at distinct cell cycle check-points. One such checkpoint occurs during mitosis, known as the spindle assembly checkpoint, and is tightly regulated through the actions of cell division cycle protein 20 (CDC20). Due to our paucity of knowledge about the role of CDC20 in the kidney, the present study was designed to investigate the expression levels and distribution of CDC20 within the kidney and how phar-macological inhibition of CDC20 function affects kidney recovery using various rodent models of kidney injury. CDC20 is nor-mally detected in distal tubules, but upon injury by either cisplatin administration or ureter obstruction, CDC20 accumulation is considerably elevated. Blockade of CDC20 activity using a selective pharmacological inhibitor, Apcin, lowered serum creatinine, tubular damage, and DNA injury following acute kidney injury compared with vehicle-treated mice. In unilateral ureteral obstruc-tion, Apcin reduced tissue kidney injury molecule-1 levels, sirius red staining, and tubulointerstitial a-smooth muscle actin staining in the tissue. The findings in the present study demonstrated that elevations in CDC20 levels in the kidney are associated with kidney injury and that inhibition of CDC20 can alleviate and reverse some of the pathological effects on the architecture and function of kidney.