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J Am Soc Nephrol 15:1452-1465, 2004
© 2004 American Society of Nephrology


BASIC SCIENCE

Angiotensin II Increases Pax-2 Expression in Fetal Kidney Cells Via the AT2 Receptor

Shao-Ling Zhang, Babak Moini and Julie R. Ingelfinger

Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, Massachusetts

Correspondence to Julie R. Ingelfinger, Harvard Medical School, Massachusetts General Hospital, Pediatric Nephrology Unit, Boston, MA 02114-3117. Phone: 617-726-5790; Fax: 617-726-3044; E-mail: jingelfinger{at}partners.org

ABSTRACT. Although both the renin angiotensin system (RAS) and the paired homeobox 2 gene (Pax-2) seem critically important in renal organogenesis, whether and how they might interact has not been addressed. The present study asked whether a link between the RAS and Pax-2 exists in fetal renal cells, speculating that such an interaction, if present, might influence renal development. Embryonic kidney explants and embryonic renal cells (mouse late embryonic mesenchymal epithelial cells [MK4] and mouse early embryonic mesenchymal fibroblasts [MK3]) were used. Pax-2 protein and Pax-2 mRNA were detected by immunofluorescence, Western blot, reverse transcription–PCR, and real-time PCR. Angiotensin II (AngII) upregulated Pax-2 protein and Pax-2 mRNA expression via the AngII type 2 (AT2) receptor in MK4 but not in MK3 cells. The stimulatory effect of AngII on Pax-2 gene expression could be blocked by PD123319 (AT2 inhibitor), AG 490 (a specific Janus kinase 2 inhibitor), and genistein (a tyrosine kinase inhibitor) but not by losartan (AT1 inhibitor), SB203580 (specific p38 mitogen-activated protein kinase inhibitor), PD98059 (specific MEK inhibitor), SP600125 (JNK inhibitor), and diphenyleneiodonium chloride (an NADPH oxidase inhibitor). Moreover, embryonic kidney explants in culture confirmed that AngII upregulates Pax-2 gene expression via the AT2 receptor. These studies demonstrate that the stimulatory effect of AngII on Pax-2 gene expression is mediated, at least in part, via the Janus kinase 2/signal transducers and activators of transcription signaling transduction pathway, suggesting that RAS and Pax-2 interactions may be important in renal development.




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