STUDIES ON THE MOLECULAR MECHANISMS OF 2,3,7,8-TETRACHLORODIBENZO-p-DIOXIN–INDUCED MORPHOLOGICAL ABNORMALITIES IN THE DEVELOPING MOUSE KIDNEY
The developing rodent kidney is one of the most sensitive tissues to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The aim of the present study was to evaluate the etiology of hydronephrosis by focusing on the mechanisms of TCDD-induced morphological abnormalities in mouse pup kidneys through measuring gene expression of several factors involved in nephrogenesis. Mouse neonates were exposed to TCDD through milk of dams that had received 15 μg TCDD/kg body weight orally after delivery. In this time-course study, the critical period of susceptibility for development of hydronephrosis was postnatal days (PND) 1–4. In the vehicle-treated mice, mRNAs for insulin-like growth factor (IGF)II, and transforming growth factor (TGF)-β were expressed at maximum levels for the first 2 days after birth and gradually decreased with advancing development. TCDD was found to cause up-regulation of TGF-β expression and down-regulation of IGFII in the early postnatal period. Furthermore, TCDD significantly up-regulated the cyclin-dependent kinase inhibitors p27kip1 and p57kip2 in developing kidneys. Studies using AhR-null mice showed that the up-regulation of p57kip2 mRNA was AhR dependent. Taken together, these data suggest that the hydronephrotic lesion caused by TCDD could be mediated by TCDD-induced G1 cell cycle arrest through mechanisms involving the AhR.
Nishimura N Miyata C Qing W Fujimaki H Nishimura H
Research Center for Environmental Risk,National Institute for Environmental Studies,Tsukuba,305-8506 Research Center for Environmental Risk,National Institute for Environmental Studies,Tsukuba,305-8506 School of Public Health,Fudan University,Shanghai,200032 China Human Sciences,Aichi Mizuho University,Toyota,470-0394 Japan
国际会议
北京
英文
1-4
2009-08-24（万方平台首次上网日期，不代表论文的发表时间）