Expression and function of the developmental gene Wnt-4 during experimental acute renal failure in rats.
The Wnt-beta-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-beta-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-beta-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 beta-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-beta-catenin pathway plays a key role in the cell cycle progression of renal tubules in ARF. The Wnt-4-beta-catenin pathway may regulate the transcription of cyclin D1 and control the regeneration of renal tubules in ARF.
Terada
Yoshio
Y
Homeostasis Medicine and Nephrology, Tokyo Medical and Dental University, 5-45 Yushima 1-chome, Bunkyo-ku, Tokyo 113-8519, Japan. yterada.kid@tmd.ac.jp
Tanaka
Hiroyuki
H
Okado
Tomokazu
T
Shimamura
Haruko
H
Inoshita
Seiji
S
Kuwahara
Michio
M
Sasaki
Sei
S
D058186:Acute Kidney Injury / Q000209:etiology / Q000503:physiopathology*; D000818:Animals; D015153:Blotting, Western; D002455:Cell Division / Q000502:physiology; D019925:Cyclin A / Q000032:analysis; D019938:Cyclin D1 / Q000032:analysis / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D007150:Immunohistochemistry; D007511:Ischemia / Q000150:complications; D018374:LLC-PK1 Cells; D008297:Male; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013552:Swine; D015534:Trans-Activators / Q000378:metabolism; D014158:Transcription, Genetic; D051153:Wnt Proteins; D060528:Wnt4 Protein; D051176:beta Catenin
C495268:Ctnnb1 protein, rat; D019925:Cyclin A; D003598:Cytoskeletal Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D060528:Wnt4 Protein; C555583:Wnt4 protein, rat; D051176:beta Catenin; D019938:Cyclin D1