Localization of the polyol pathway in the human kidney
Steffen Zopf1, Jakob Flämig2, Heide Schmid3, Nicolai Miosge4, Sabine Blaschke2, Eckhart G. Hahn1, Gerhard A. Müller2 and Rolf W. Grunewald2,5
1Department of Internal Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany, 2Department of Nephrology and Rheumatology, University of Goettingen, Goettingen, Germany, 3Department of Pathology, University of Tuebingen, Tuebingen, Germany, 4Department of Anatomy, University of Goettingen, Goettingen, Germany and 5Department of Internal Medicine I, St. Antonius Hospital Kleve, Kleve, Germany.
Offprint requests to: Steffen Zopf, MD, Department of Medicine 1, University of Erlangen-Nuremberg, Ulmenweg 18, D-91054 Erlangen, Germany. e-mail: steffen.zopf@uk-erlangen.de
Summary. Sorbitol plays an important role in the osmotic regulation of the mammalian kidney. Sorbitol synthesis is regulated by the enzyme aldose reductase (AR) and its degradation to fructose is catalyzed by the enzyme sorbitol dehydrogenase (SDH). Various data exist on the polyol pathway on the rat kidney, but little is known about the distribution of the polyol pathway enzymes in the human kidney. Determination of enzyme activities and a semiquantitative determination of mRNA expression, immunohistochemistry and in-situ hybridisation in healthy human kidney tissue was carried out. The enzyme activity of AR showed a fourfold increase from cortex to papilla, while SDH-activity dropped from cortex to papilla by a factor of four. Corresponding data was obtained at the mRNA level from the semiquantitative polymerase chain reaction (PCR). Additional differentiation at the cellular level reveals both enzymes in cells of the proximal and distal tubules, thick ascending loop, thin loop and collecting duct. Studies of enzyme activity and expression by immunohistochemistry, PCR and in-situ hybridization presented corresponding results with respect to the localization of the enzymes, which match the experimental data obtained from rats very well. Thus, the established rat model might well represent the situation in the human kidney, too. Histol Histopathol 24, 447-455 (2009)
Key words: Polyol pathway, Aldose reductase, Sorbitol dehydrogenase, Human kidney
DOI: 10.14670/HH-24.447