title: Renal tubular fluid shear stress promotes endothelial cell activation.
abstract: Modified urinary fluid shear stress (FSS) induced by variations of urinary fluid flow and composition is observed in early phases of most kidney diseases. In this study, we hypothesized that changes in urinary FSS represent a tubular aggression that contributes to the development of inflammation, a key event in progression of nephropathies. Human renal tubular cells (HK-2) were exposed to FSS for 30 min at 0.01 Pa. Treatment of human endothelial cells (HMEC-1) with the resulting conditioned medium (FSS-CM) increased C-C chemokine ligand 2 (CCL2) and tumor necrosis factor (TNF)-α protein secretion, increased endothelial vascular adhesion molecule-1 (VCAM-1) mRNA expression and stimulated adhesion of human (THP-1) monocytes to the endothelial monolayer. These effects were TNF-α dependent as they were abolished by neutralization of TNF-α. Interestingly, the origin of TNF-α was not epithelial, but resulted from autocrine endothelial production. However, in contrast to short term FSS, long term FSS (5h) induced the release of the key inflammatory proteins CCL2 and TNF-α directly from tubular cells. In conclusion, these results suggest for the first time that urinary FSS can contribute to the inflammatory state involved in initiation/perpetuation of renal diseases.
authors: Institut National de Santé et de Recherche Médicale (INSERM), U1048, Toulouse, France.
authors: Mathieu
authors: M
authors: Miravète
authors: Julie
authors: J
authors: Klein
authors: Aurèle
authors: A
authors: Besse-Patin
authors: Julien
authors: J
authors: Gonzalez
authors: Christiane
authors: C
authors: Pecher
authors: Jean-Loup
authors: JL
authors: Bascands
authors: Muriel
authors: M
authors: Mercier-Bonin
authors: Joost P
authors: JP
authors: Schanstra
authors: Bénédicte
authors: B
authors: Buffin-Meyer
mesh_terms: D002448:Cell Adhesion; D018932:Chemokine CCL2 / Q000096:biosynthesis; D017077:Culture Media, Conditioned / Q000494:pharmacology; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D007684:Kidney Tubules / Q000166:cytology* / Q000187:drug effects; D009000:Monocytes / Q000502:physiology; D033081:Shear Strength; D013314:Stress, Mechanical; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D014556:Urine / Q000502:physiology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
chemical_list: D018932:Chemokine CCL2; D017077:Culture Media, Conditioned; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1