Keratins are novel markers of renal epithelial cell injury
Standard
Keratins are novel markers of renal epithelial cell injury. / Djudjaj, Sonja; Papasotiriou, Marios; Bülow, Roman D; Wagnerova, Alexandra; Lindenmeyer, Maja T; Cohen, Clemens D; Strnad, Pavel; Goumenos, Dimitrios S; Floege, Jürgen; Boor, Peter.
In: KIDNEY INT, Vol. 89, No. 4, 04.2016, p. 792-808.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Keratins are novel markers of renal epithelial cell injury
AU - Djudjaj, Sonja
AU - Papasotiriou, Marios
AU - Bülow, Roman D
AU - Wagnerova, Alexandra
AU - Lindenmeyer, Maja T
AU - Cohen, Clemens D
AU - Strnad, Pavel
AU - Goumenos, Dimitrios S
AU - Floege, Jürgen
AU - Boor, Peter
N1 - Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.
PY - 2016/4
Y1 - 2016/4
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - Aged, 80 and over
KW - Animals
KW - Biomarkers
KW - Case-Control Studies
KW - Epithelial Cells
KW - Female
KW - Humans
KW - Keratin-18
KW - Keratins
KW - Kidney
KW - Kidney Diseases
KW - Male
KW - Mice, Inbred C57BL
KW - Phosphorylation
KW - Ureteral Obstruction
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1016/j.kint.2015.10.015
DO - 10.1016/j.kint.2015.10.015
M3 - SCORING: Journal article
C2 - 26924053
VL - 89
SP - 792
EP - 808
JO - KIDNEY INT
JF - KIDNEY INT
SN - 0085-2538
IS - 4
ER -