title: Kidney Injury Molecule-1 Is Specifically Expressed in Cystically-Transformed Proximal Tubules of the PKD/Mhm (cy/+) Rat Model of Polycystic Kidney Disease.
abstract: Expression of kidney injury molecule-1 (Kim-1) is rapidly upregulated following tubular injury, constituting a biomarker for acute kidney damage. We examined the renal localization of Kim-1 expression in PKD/Mhm (polycystic kidney disease, Mannheim) (cy/+) rats (cy: mutated allel, +: wild type allel), an established model for autosomal dominant polycystic kidney disease, with chronic, mainly proximal tubulointerstitial alterations. For immunohistochemistry or Western blot analysis, kidneys of male adult heterozygously-affected (cy/+) and unaffected (+/+) littermates were perfusion-fixed or directly removed. Kim-1 expression was determined using peroxidase- or fluorescence-linked immunohistochemistry (alone or in combination with markers for tubule segments or differentiation). Compared to (+/+), only in (cy/+) kidneys, a chronic expression of Kim-1 could be detected by Western blot analysis, which was histologically confined to an apical cellular localization in areas of cystically-transformed proximal tubules with varying size and morphology, but not in distal tubular segments. Kim-1 was expressed by cystic epithelia exhibiting varying extents of dedifferentiation, as shown by double labeling with aquaporin-1, vimentin or osteopontin, yielding partial cellular coexpression. In this model, in contrast to other known molecules indicating renal injury and/or repair mechanisms, the chronic renal expression of Kim-1 is strictly confined to proximal cysts. Its exact role in interfering with tubulo-interstitial alterations in polycystic kidney disease warrants future investigations.
authors.affiliation: Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany. gauer@em.uni-frankfurt.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Gauer
authors.affiliation: Department of Urology and Paediatric Urology, Philipps-University Marburg, 35043 Marburg, Germany. anja.urbschat@staff.uni-marburg.de.
authors.forename: Anja
authors.initials: A
authors.lastname: Urbschat
authors.affiliation: Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany. norbert.gretz@medma.uni-heidelberg.de.
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.affiliation: Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany. sigrid.hoffmann@medma.uni-heidelberg.de.
authors.forename: Sigrid C
authors.initials: SC
authors.lastname: Hoffmann
authors.affiliation: Medical Research Center, University of Heidelberg, 68167 Mannheim, Germany. bettina.kraenzlin@medma.uni-heidelberg.de.
authors.forename: Bettina
authors.initials: B
authors.lastname: Kränzlin
authors.affiliation: Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany. helmut.geiger@kgu.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Geiger
authors.affiliation: Division of Nephrology, III. Medical Clinic, University Hospital Frankfurt, Goethe-University, 60590 Frankfurt, Germany. obermueller@em.uni-frankfurt.de.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Obermüller
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D054337:Cell Dedifferentiation; D004195:Disease Models, Animal; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009928:Organ Specificity; D007690:Polycystic Kidney Diseases / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; C110936:Havcr1 protein, rat
keywords: Kim-1; dedifferentiation; polycystic kidney; proximal tubule; rat model