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Received February 21, 2006
Accepted on July 10, 2006

BASIC SCIENCE: Cell and Transport Physiology

Expression of the Ammonia Transporter, Rh C Glycoprotein, in Normal and Neoplastic Human Kidney

Ki-Hwan Han ^*, Byron P. Croker , William L. Clapp , Dietrich Werner , Manisha Sahni , Jin Kim ^||, Hye-Young Kim , Mary E. Handlogten , and I. David Weiner ^¶1

*Department of Anatomy, Ewha Womans University, Seoul, Korea; Department of Pathology and Division of Nephrology, Hypertension and Transplantation, University of Florida, and Department of Pathology and ¶Nephrology Section, North Florida/South Georgia Veterans Health System, Gainesville, Florida; and ||Department of Anatomy and Medical Research Center for Cell Death Disease Research Center, The Catholic University of Korea, Seoul, Korea

¹ To whom correspondence should be addressed. E-mail: weineid{at}ufl.edu.

	Abstract

Recent studies have identified the presence of a novel Mep/Amt/Rh glycoprotein family of proteins that may play an important role in transmembrane ammonia transport. One of the mammalian members of this family, Rh C glycoprotein (RhCG), transports ammonia, is expressed in distal nephron sites that are critically important for ammonia secretion, exhibits increased expression in response to chronic metabolic acidosis, and originally was cloned as a tumor-related protein. The purpose of our studies was to determine the localization of RhCG in the normal and neoplastic human kidney. Immunoblot analysis of human renal cortical protein lysates demonstrated RhCG protein expression with a molecular weight of approximately 52 kD. Immunohistochemistry revealed both apical and basolateral Rhcg expression in the distal convoluted tubule, connecting segment, and initial collecting tubule and throughout the collecting duct. Co-localization with calbindin-D28k, H⁺-ATPase, aquaporin-2, and pendrin showed that distal convoluted tubule and connecting segment cells, A-type intercalated cells, and non-A, non-B cells express RhCG and that B-type intercalated cells, principal cells, and inner medullary collecting duct cells do not. In renal neoplasms, RhCG was expressed by chromophobe renal cell carcinoma and renal oncocytoma but not by clear cell renal cell carcinoma or by papillary renal cell carcinomas. These studies suggest that RhCG contributes to both apical and basolateral membrane ammonia transport in the human kidney. Furthermore, renal chromophobe renal cell carcinoma and renal oncocytoma seem to originate from the A-type intercalated cell.

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Copyright © 2009 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673