Kidney Tubular Cell Regeneration Starts in the Deep Cortex after Ischemia / 대한신장학회지

ABSTRACT

PURPOSE: In kidneys exposed to ischemia/reperfusion (I/R), the periodic and regional changes of loss and restoration of tubular epithelial cells and the influence of these processes for renal function remain to be defined. We investigated the loss and regeneration of tubular cells in each nephron segment at various times after I/R. METHODS: Mice were subjected to 30 min of bilateral renal ischemia and were administered 5-bromo-2'-deoxyuridine (BrdU) 20 hours before harvest kidneys. The numbers of tubular cell nuclei, BrdUincorporating cells and proliferative cell nuclear antigen (PCNA)-positive cells were analyzed by PASstaining and immunohistochemistry. RESULTS: Thirty minutes of ischemia induced loss of tubular epithelial cells in the outer stripe of the outer medulla. The loss of tubular epithelial cells peaked 24 hours after ischemia. After the maximum decrease, recovery of number of tubular epithelial cells was observed from 3 days after I/R in the outer medulla and from 5 days in the cortex. The tubular cell numbers were inversely correlated with the changes in concentrations of plasma creatinine and BUN by Pearson correlation, indicating that the decrease and increase of tubular epithelial cell numbers reflect functional failure and recovery, respectively. Cell proliferation as determined by BrdU-incorporating appeared in the deep cortex from 3 days after ischemia. CONCLUSION: The recovery of renal function was found to significantly correlate with the restoration of tubular cells. Furthermore, the regeneration of tubular cells started in the tubules of the deep cortex, suggesting that it may be a great proliferative cell niche.