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Expression and Function of the Developmental Gene Wnt-4 during Experimental Acute Renal Failure in Rats

Homeostasis Medicine and Nephrology, Tokyo Medical and Dental University, Tokyo, Japan.

Correspondence to Dr. Yoshio Terada, Homeostasis Medicine and Nephrology, Tokyo Medical and Dental University, 5-45, Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan. Phone: 81-3-5803-5214; Fax: 81-3-5803-5215;

ABSTRACT. The Wnt--catenin pathway plays key roles in embryogenesis. Wnt-4 is known to be expressed in the mesonephric duct in embryonic development. It is tempting to speculate that the Wnt-4--catenin pathway contributes to the recovery from acute renal failure (ARF). This study used an in vivo model of ARF rats to clarify the significance of the Wnt-4--catenin pathway in ARF. ARF was induced by clamping the rat left renal artery for 1 h. At 3, 6, 12, 24, 48, and 72 h after reperfusion, whole kidney homogenate and total RNA were extracted for examination by Western blot analysis and real-time RT-PCR. Wnt-4 mRNA and protein expression were strongly increased at 3 to 12 h and 6 to 24 h after ischemia, respectively. In immunohistologic examination, Wnt-4 was expressed in the proximal tubules and co-expressed with aquaporin-1, GM130, and PCNA. Cyclin D1 and cyclin A were expressed at 24 to 48 h after reperfusion. In addition, the overexpression of Wnt-4 and -catenin promoted the cell cycle and increased the promoter activity and protein expression of cyclin D1 in LLC-PK1 cells. Taken together, these data suggest that the Wnt-4--catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Wnt-4--catenin pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF. E-Mail: yterada.kid@tmd.ac.jp

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