Renal tubular fluid shear stress promotes endothelial cell activation

• Published in: Biochemical and biophysical research communications 2011-04, Vol.407 (4), p.813-817
• Main Authors: Miravète, Mathieu, Klein, Julie, Besse-Patin, Aurèle, Gonzalez, Julien, Pecher, Christiane, Bascands, Jean-Loup, Mercier-Bonin, Muriel, Schanstra, Joost P., Buffin-Meyer, Bénédicte
• Format: Article
• Language: English
• Subjects: Cell Adhesion; Chemokine CCL2; Chemokine CCL2 - biosynthesis; Culture Media, Conditioned; Culture Media, Conditioned - pharmacology; Endothelial cell activation; Endothelial Cells; Endothelial Cells - drug effects; Endothelial Cells - physiology; Humans; Hydrodynamic forces; Inflammation; Inflammation - physiopathology; Kidney Diseases; Kidney Diseases - physiopathology; Kidney Tubules; Kidney Tubules - cytology; Kidney Tubules - drug effects; Mechanical insult; Monocytes; Monocytes - physiology; Renal tubular damage; Shear Strength; Stress, Mechanical; Tumor Necrosis Factor-alpha; Tumor Necrosis Factor-alpha - antagonists & inhibitors; Tumor Necrosis Factor-alpha - biosynthesis; Urine; Urine - physiology; Vascular Cell Adhesion Molecule-1; Vascular Cell Adhesion Molecule-1 - biosynthesis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2011.03.105

► Urinary shear stress is modified in most kidney diseases. ► Urinary shear stress is an aggressor of renal tubular cells. ► We showed for the first time that urinary shear stress promotes inflammation. ► Urinary shear stress is potentially a new actor in the progression of renal pathologies. 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 30min at 0.01Pa. 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.