Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure
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Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure. / Koziolek, Michael J; Müller, Gerhard-Anton; Zapf, Antonia; Patschan, Daniel; Schmid, Holger; Cohen, Clemens D; Koschnick, Stefan; Vasko, Radovan; Bramlage, Carsten; Strutz, Frank.
in: NEPHROL DIAL TRANSPL, Jahrgang 25, Nr. 3, 03.2010, S. 684-698.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Role of CX3C-chemokine CX3C-L/fractalkine expression in a model of slowly progressive renal failure
AU - Koziolek, Michael J
AU - Müller, Gerhard-Anton
AU - Zapf, Antonia
AU - Patschan, Daniel
AU - Schmid, Holger
AU - Cohen, Clemens D
AU - Koschnick, Stefan
AU - Vasko, Radovan
AU - Bramlage, Carsten
AU - Strutz, Frank
PY - 2010/3
Y1 - 2010/3
N2 - BACKGROUND: The chemokine/chemokine receptor pair CX(3)C-L/CX(3)C-R is suspected to play a role in renal fibrogenesis. The aim of this study was to investigate their function in an animal model of slowly progressive chronic renal failure.METHODS: Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction). Immunostaining for CX(3)C-L, CD3, S100A4, collagen type I, fibronectin, alpha-smooth muscle actin, Tamm-horsfall protein, aquaporin 1 and 2 as well as quantitative real-time PCR (qRT-PCR) for CX(3)C-L, CX(3)C-R and fibroblast-specific protein 1 (FSP-1) were performed. Additionally, regulatory mechanisms and functional activity of CX(3)C-L in murine proximal and distal tubular epithelial cells as well as in fibroblasts were investigated.RESULTS: CX(3)C-L/GAPDH ratio was upregulated in FAN 3.4-fold at day 7 further increasing up to 7.1-fold at day 106. The expression of mRNA CX(3)C-L correlated well with CX(3)C-R (R(2) = 0.96), the number of infiltrating CD3+ cells (R(2) = 0.60) and the degree of tubulointerstitial fibrosis (R(2) = 0.56) and moderately with FSP-1 (R(2) = 0.33). Interleukin-1beta, tumour necrosis factor-alpha, transforming growth factor-beta as well as the reactive oxygen species (ROS) H(2)O(2) were identified by qRT-PCR as inductors of CX(3)C-L/fractalkine (FKN) in tubular epithelial cells. Functionally, CX(3)C-L/FKN chemoattracts peripheral blood mononuclear cells, activates several aspects of fibrogenesis and induces the mitogen-activated protein kinases in renal fibroblasts.CONCLUSIONS: In FAN, there is a good correlation between the expression of CX(3)C-L with markers of interstitial inflammation and fibrosis which may result from upregulation by pro-inflammatory and pro-fibrotic cytokines as well as by ROS in tubular epithelial cells. The FKN system may promote renal inflammation and renal fibrogenesis.
AB - BACKGROUND: The chemokine/chemokine receptor pair CX(3)C-L/CX(3)C-R is suspected to play a role in renal fibrogenesis. The aim of this study was to investigate their function in an animal model of slowly progressive chronic renal failure.METHODS: Functional data were analysed in folic acid nephropathy (FAN) at different time points (up to day 142 after induction). Immunostaining for CX(3)C-L, CD3, S100A4, collagen type I, fibronectin, alpha-smooth muscle actin, Tamm-horsfall protein, aquaporin 1 and 2 as well as quantitative real-time PCR (qRT-PCR) for CX(3)C-L, CX(3)C-R and fibroblast-specific protein 1 (FSP-1) were performed. Additionally, regulatory mechanisms and functional activity of CX(3)C-L in murine proximal and distal tubular epithelial cells as well as in fibroblasts were investigated.RESULTS: CX(3)C-L/GAPDH ratio was upregulated in FAN 3.4-fold at day 7 further increasing up to 7.1-fold at day 106. The expression of mRNA CX(3)C-L correlated well with CX(3)C-R (R(2) = 0.96), the number of infiltrating CD3+ cells (R(2) = 0.60) and the degree of tubulointerstitial fibrosis (R(2) = 0.56) and moderately with FSP-1 (R(2) = 0.33). Interleukin-1beta, tumour necrosis factor-alpha, transforming growth factor-beta as well as the reactive oxygen species (ROS) H(2)O(2) were identified by qRT-PCR as inductors of CX(3)C-L/fractalkine (FKN) in tubular epithelial cells. Functionally, CX(3)C-L/FKN chemoattracts peripheral blood mononuclear cells, activates several aspects of fibrogenesis and induces the mitogen-activated protein kinases in renal fibroblasts.CONCLUSIONS: In FAN, there is a good correlation between the expression of CX(3)C-L with markers of interstitial inflammation and fibrosis which may result from upregulation by pro-inflammatory and pro-fibrotic cytokines as well as by ROS in tubular epithelial cells. The FKN system may promote renal inflammation and renal fibrogenesis.
KW - Animals
KW - Calcium-Binding Proteins
KW - Cell Line
KW - Cells, Cultured
KW - Chemokine CX3CL1
KW - Chemokines, CX3C
KW - Cytokines
KW - Disease Models, Animal
KW - Disease Progression
KW - Female
KW - Fibrosis
KW - Folic Acid
KW - Humans
KW - Kidney Tubules, Distal
KW - Kidney Tubules, Proximal
KW - Mice
KW - Mice, Inbred Strains
KW - Reactive Oxygen Species
KW - Renal Insufficiency
KW - S100 Calcium-Binding Protein A4
KW - S100 Proteins
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/ndt/gfp602
DO - 10.1093/ndt/gfp602
M3 - SCORING: Journal article
C2 - 19934081
VL - 25
SP - 684
EP - 698
JO - NEPHROL DIAL TRANSPL
JF - NEPHROL DIAL TRANSPL
SN - 0931-0509
IS - 3
ER -
