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Originally published as JHC exPRESS on November 14, 2005.
doi:10.1369/jhc.5A6815.2005
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Journal of Histochemistry and Cytochemistry
Volume 54 (2): 253-262, 2006
Copyright ©The Histochemical Society, Inc.

Expression and Effect of Inhibition of Aminopeptidase-A during Nephrogenesis

Henry B.P.M. Dijkman, Karel J.M. Assmann, Eric J. Steenbergen and Jack F.M. Wetzels

Department of Pathology (HBPMD, KJMA, EJS) and Department of Internal Medicine, Division of Nephrology (JFMW), Radboud University Nijmegen Medical Centre, The Netherlands

Correspondence to: H.B.P.M Dijkman, Department of Pathology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: h.dijkman{at}pathol.umcn.nl

Aminopeptidase-A (APA) is a metalloprotease that cleaves N-terminal aspartyl and glutamyl residues from peptides. Its best-known substrate is angiotensin II (Ang II), the most active compound of the renin–angiotensin system (RAS). The RAS is involved in renal development. Most components of the RAS system are expressed in the developing kidney. Thus far, APA has not been studied in detail. In the present study we have evaluated the expression of APA at the protein, mRNA, and enzyme activity (EA) level in the kidney during nephrogenesis. Furthermore, we have studied the effect of inhibiting APA EA by injection of anti-APA antibodies into 1-day-old mice. APA expression was observed from the comma stage onwards, predominantly in the developing podocytes and brush borders of proximal tubular cells. Notably, APA was absent in the medulla or the renal arterioles. Inhibition of APA EA caused temporary podocyte foot-process effacement, suggesting a minimum role for APA during nephrogenesis. (J Histochem Cytochem 54:253–262, 2006)

Key Words: podocyte • nephrogenesis • aminopeptidase-A • albuminuria • monoclonal antibodies • inhibition • enzyme activity • mouse


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