title: Keratins are novel markers of renal epithelial cell injury.
abstract: Keratins, the intermediate filaments of the epithelial cell cytoskeleton, are up-regulated and post-translationally modified in stress situations. Renal tubular epithelial cell stress is a common finding in progressive kidney diseases, but little is known about keratin expression and phosphorylation. Here, we comprehensively describe keratin expression in healthy and diseased kidneys. In healthy mice, the major renal keratins, K7, K8, K18, and K19, were expressed in the collecting ducts and K8, K18 in the glomerular parietal epithelial cells. Tubular expression of all 4 keratins increased by 20- to 40-fold in 5 different models of renal tubular injury as assessed by immunohistochemistry, Western blot, and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The up-regulation became significant early after disease induction, increased with disease progression, was found de novo in distal tubules and was accompanied by altered subcellular localization. Phosphorylation of K8 and K18 increased under stress. In humans, injured tubules also exhibited increased keratin expression. Urinary K18 was only detected in mice and patients with tubular cell injury. Keratins labeled glomerular parietal epithelial cells forming crescents in patients and animals. Thus, all 4 major renal keratins are significantly, early, and progressively up-regulated upon tubular injury regardless of the underlying disease and may be novel sensitive markers of renal tubular cell stress.
authors.affiliation: Division of Nephrology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany; Institute of Pathology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Djudjaj
authors.affiliation: Division of Nephrology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany; Department of Nephrology, University Hospital of Patras, Patras, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Papasotiriou
authors.affiliation: Institute of Pathology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Roman D
authors.initials: RD
authors.lastname: Bülow
authors.affiliation: Institute of Pathology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Wagnerova
authors.affiliation: Division of Nephrology and Institute of Physiology, University Zürich, Zürich, Switzerland.
authors.forename: Maja T
authors.initials: MT
authors.lastname: Lindenmeyer
authors.affiliation: Division of Nephrology and Institute of Physiology, University Zürich, Zürich, Switzerland.
authors.forename: Clemens D
authors.initials: CD
authors.lastname: Cohen
authors.affiliation: Department of Internal Medicine 3 and Interdisziplinäres Zentrum für Klinische Forschung, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Pavel
authors.initials: P
authors.lastname: Strnad
authors.affiliation: Department of Nephrology, University Hospital of Patras, Patras, Greece.
authors.forename: Dimitrios S
authors.initials: DS
authors.lastname: Goumenos
authors.affiliation: Division of Nephrology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Floege
authors.affiliation: Division of Nephrology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany; Institute of Pathology, Rheinisch-Westfälische Technische Hochschule Aachen, Aachen, Germany; Institute of Molecular Biomedicine, Comenius University, Bratislava, Slovakia. Electronic address: pboor@ukaachen.de.
authors.forename: Peter
authors.initials: P
authors.lastname: Boor
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D053538:Keratin-18 / Q000652:urine; D007633:Keratins / Q000378:metabolism*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D010766:Phosphorylation; D014517:Ureteral Obstruction / Q000378:metabolism
chemical_list: D015415:Biomarkers; D053538:Keratin-18; D007633:Keratins
keywords: chronic kidney disease; renal pathology; tubular cells