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Start Over Descriptor "podocyte adhesion" Journal kidney international
2 results on '"podocyte adhesion"'

1. Biomechanical strain causes maladaptive gene regulation, contributing to Alport glomerular disease.

Author

Meehan, Daniel T., Delimont, Duane, Cheung, Linda, Zallocchi, Marisa, Sansom, Steven C., Holzclaw, J. David, Rao, Velidi, and Cosgrove, Dominic

Subjects
*ALPORT syndrome, *TREATMENT of chronic kidney failure, *INTERLEUKIN-6, *PROTEINURIA, *GENETIC regulation, *PATIENTS, *THERAPEUTICS, *DISEASE risk factors
Abstract

Patients with Alport's syndrome develop a number of pro-inflammatory cytokine and matrix metalloproteinase (MMP) abnormalities that contribute to progressive renal failure. Changes in the composition and structure of the glomerular basement membranes likely alter the biomechanics of cell adhesion and signaling in these patients. To test if enhanced strain on the capillary tuft due to these structural changes contributes to altered gene regulation, we subjected cultured podocytes to cyclic biomechanical strain. There was robust induction of interleukin (IL)-6, along with MMP-3, -9, -10, and -14, but not MMP-2 or -12 by increased strain. Neutralizing antibodies against IL-6 attenuated the strain-mediated induction of MMP-3 and -10. Alport mice treated with a general inhibitor of nitric oxide synthase (L-NAME) developed significant hypertension and increased IL-6 and MMP-3 and -10 in their glomeruli relative to those of normotensive Alport mice. These hypertensive Alport mice also had elevated proteinuria along with more advanced histological and ultrastructural glomerular basement membrane damage. We suggest that MMP and cytokine dysregulation may constitute a maladaptive response to biomechanical strain in the podocytes of Alport patients, thus contributing to glomerular disease initiation and progression. [ABSTRACT FROM AUTHOR]

Published
2009
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2. Biomechanical strain causes maladaptive gene regulation, contributing to Alport glomerular disease

Author

Duane Delimont, Velidi H. Rao, Dominic Cosgrove, Steven C. Sansom, Marisa Zallocchi, Linda Cheung, J. David Holzclaw, and Daniel T. Meehan

Subjects
medicine.medical_specialty, Time Factors, Renal glomerulus, Kidney Glomerulus, Blood Pressure, Nephritis, Hereditary, Biology, urologic and male genital diseases, Article, Podocyte, Mice, podocyte adhesion, Matrix Metalloproteinase 10, Internal medicine, Glomerular Basement Membrane, medicine, Matrix Metalloproteinase 14, Animals, RNA, Messenger, Alport syndrome, Sodium Chloride, Dietary, Interleukin 6, Cells, Cultured, Cytoskeleton, Kidney, Interleukin-6, Podocytes, Glomerular basement membrane, Glomerulonephritis, medicine.disease, Adaptation, Physiological, female genital diseases and pregnancy complications, Matrix Metalloproteinases, Mice, Inbred C57BL, Disease Models, Animal, Proteinuria, medicine.anatomical_structure, Endocrinology, NG-Nitroarginine Methyl Ester, Gene Expression Regulation, Matrix Metalloproteinase 9, Nephrology, Hypertension, biology.protein, biomechanical strain, Matrix Metalloproteinase 3, Stress, Mechanical, Nephritis
Abstract

Alport glomerular disease is associated with dysregulation of pro-inflammatory cytokines and matrix metalloproteinases, promoting progressive glomerulonephritis. Changes in composition and structure of Alport GBM resulting from mutations in type IV collagen genes likely alter cell adhesion and cell signaling. Enhanced biomechanical strain on the capillary tuft, resulting from a thinner and less crosslinked GBM may be a source of insult which contributes to gene dysregulation. To test this we subjected cultured podocytes to cyclic biomechanical strain. We observed robust induction of MMP-3, −9, −10, and −14, but not MMP-2 or MMP-12. IL-6 was induced by biomechanical strain, and neutralizing antibodies against IL-6 attenuated induction of MMP-3 and MMP-10. Alport mice given L-NAME salts, which resulted in a significant rise in systolic blood pressure, showed Induction of MMP-3, MMP-10, and IL-6 in glomeruli relative to normotensive Alport mice. Hypertensive Alport mice also had elevated proteinuria, and more advanced GBM disease histologically and ultrastucturally. Collectively these data suggest MMP and cytokine dysregulation may constitute a maladaptive response to biomechanical strain in Alport podocytes, and that this response may contribute to the mechanism of glomerular disease initiation and progression.

Published
2009

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