Korean Journal of Nephrology 2008;27(5):536-544.
Kidney Tubular Cell Regeneration Starts in the Deep Cortex after Ischemia
Jinu Kim, M.S.1, Jee In Kim, D.V.M., Ph.D.2, Tae-Hwan Kwon, M.D., Ph.D.3 and Kwon Moo Park, D.V.M., Ph.D.1
Department of Anatomy and Brain Korea 21 Project1
Kyungpook National University School of Medicine, Daegu Korea, Department of Molecular Physiology and Biophysics2
Thomas Jefferson University Jefferson Medical College, JAH Room 436
1020 Locust Street, Philadelphia, PA19107
USA, Department of Biochemistry and Cell Biology3
Kyungpook National University School of Medicine, Daegu Korea
원저 : Kidney Tubular Cell Regeneration Starts in the Deep Cortex after Ischemia
Jinu Kim, M.S.1, Jee In Kim, D.V.M., Ph.D.2, Tae-Hwan Kwon, M.D., Ph.D.3 and Kwon Moo Park, D.V.M., Ph.D.1
Department of Anatomy and Brain Korea 21 Project1, Kyungpook National University School of Medicine, Daegu Korea, Department of Molecular Physiology and Biophysics2, Thomas Jefferson University Jefferson Medical College, JAH Room 436, 1020 Locust Street,
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.
Key Words: Ischemia, Cell proliferation, Regeneration, Bromodeoxyuridine, Proliferating cell nuclear
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