P53 inhibitor pifithrin-α prevents the renal tubular epithelial cells against injury.
The injury and repair of renal tubular epithelial cells play an important role in the pathological process of acute kidney injury (AKI). This study aimed to clarify the role of cell cycle change in renal tubular epithelial cell injury and repairin vivoandin vitro. Sprague-Dawley rats received bilateral renal pedicle clamping for 45 min (ischemia) followed by reperfusion. Pifithrin-α, a p53 inhibitor, was administered at 24 h before renal ischemia and 3 and 14 days after reperfusion. Results showed the tubular epithelial cells in M phase increased significantly at 2 h to 72 h after ischemia/reperfusion (I/R), while pifithrin-α decreased them. Renal I/R caused renal tubular epithelial damage in rats, which was improved by pifithrin-α. The α-SMA mRNA expression was up-regulated significantly after I/R, while it was down-regulated by pifithrin-α.NRK-52E cells were culturedin vitro, cell damage was induced by addition of TNF-α, and then cells were treated with pifithrin-α. Cells treated with TNF-α alone in G2/M phase increased significantly, but they were reduced in the presence of pifithrin-α. In NRK-52E cells treated with pifithrin-α for 6 h, NGAL mRNA expression was significantly lower than in cells without pifithrin-α treatment. After NRK-52E cells were treated with pifithrin-α for 24 h, α-SMA and FN mRNA expression was significantly lower than in cells without the treatment. In summary, pifithrin-α can facilitate the progression of renal tubular epithelial cells through G2/M phase, protecting them against injury.
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Yun-Lin
YL
Shen
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Lei
L
Sun
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Yu-Jie
YJ
Hu
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Hua-Jie
HJ
Liu
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Xin-Yu
XY
Kuang
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Xiao-Ling
XL
Niu
Department of Nephrology and Rheumatology, Shanghai Children's Hospital, Shanghai Jiao Tong University Shanghai 200062, China.
Wen-Yan
WY
Huang
Acute kidney injury (AKI); G2/M phase; cell cycle; pifithrin-α; renal tubular epithelial cell