Pax-2 and N-myc regulate epithelial cell proliferation and apoptosis in a positive autocrine feedback loop.
Both paired homeo box-2 (Pax-2) and N-myc genes play pivotal roles in renal morphogenesis via their effects on cell proliferation and differentiation, but whether and how they interact have not been addressed. In the present study, we investigated such a potential interaction using embryonic renal cells in vitro. Mouse embryonic mesenchymal (MK4) cells stably transfected with Pax-2 cDNA in sense (+) or antisense (-) orientation were used for experiments. Pax-2 promoter activity was monitored by luciferase assay. Reactive oxygen species (ROS) generation, cell proliferation, and cell apoptosis were evaluated. We found that Pax-2 and N-myc gene expression were upregulated and downregulated in Pax-2 (+) and Pax-2 (-) stable transformants, respectively. ROS generation and apoptosis were significantly reduced both in Pax-2 (+) transformants compared with Pax-2 (-) transformants and in naïve MK4 cells cultured in either normal- (5 mM) or high-glucose (25 mM) medium. Transient transfection of N-myc cDNA into Pax-2 (-) stable transformants restored Pax-2 gene expression and prevented ROS generation induced by high glucose. Our data demonstrate that Pax-2 gene overexpression prevents hyperglycemia-induced apoptosis, and N-myc appears to provide a positive autocrine feedback on Pax-2 gene expression in embryonic mesenchymal cells.
Zhang
Shao-Ling
SL
University of Montréal, Centre hospitalier de l'Université de Montréal (CHUM)- Hôtel-Dieu, 3850 Saint Urbain Street, Montréal, Québec, H2W 1T7, Canada. shao.ling.zhang@umontreal.ca
Chen
Yun-Wen
YW
Tran
Stella
S
Liu
Fang
F
Nestoridi
Eirini
E
Hébert
Marie-Josée
MJ
Ingelfinger
Julie R
JR
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019898:Autocrine Communication / Q000502:physiology; D002460:Cell Line; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism / Q000473:pathology; D025461:Feedback, Physiological; D018507:Gene Expression Regulation, Developmental; D007668:Kidney / Q000196:embryology; D008648:Mesoderm / Q000166:cytology / Q000378:metabolism; D051379:Mice; D051762:PAX2 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection
D051762:PAX2 Transcription Factor; C497319:Pax2 protein, mouse; D016271:Proto-Oncogene Proteins c-myc; D017382:Reactive Oxygen Species