Similar Biophysical Abnormalities in Glomeruli and Podocytes from Two Distinct Models
| Autor: | Olaf Stüve, Zhenzhen Wu, Zhenan Liu, Leslie A. Bruggeman, C. Barton Gillombardo, F. Jefferson Byfield, Rihanna Z. Hussain, Audrey N. Chang, R. Tyler Miller, Joonho Yoon, Liping Liu, Sara Moradi, Paul A. Janmey, Richard Doelger, Addie E. Embry, Joel M. Henderson, Katrina Cruz |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Kidney Glomerulus Mice Transgenic Glomerulus (kidney) Microscopy Atomic Force Real-Time Polymerase Chain Reaction Biophysical Phenomena Podocyte Focal adhesion Mice 03 medical and health sciences Glomerulonephritis Elastic Modulus Cell Adhesion medicine Renal fibrosis Animals Protamines Cytoskeleton biology Podocytes Chemistry Nephrosis Lipoid HIV General Medicine Adhesion Protamine Cell biology Disease Models Animal Basic Research 030104 developmental biology medicine.anatomical_structure Microscopy Fluorescence Nephrology Disease Progression Slit diaphragm biology.protein Collagen Paxillin |
| Zdroj: | Journal of the American Society of Nephrology. 29:1501-1512 |
| ISSN: | 1533-3450 1046-6673 |
| DOI: | 10.1681/asn.2017050475 |
| Popis: | Background FSGS is a pattern of podocyte injury that leads to loss of glomerular function. Podocytes support other podocytes and glomerular capillary structure, oppose hemodynamic forces, form the slit diaphragm, and have mechanical properties that permit these functions. However, the biophysical characteristics of glomeruli and podocytes in disease remain unclear. Methods Using microindentation, atomic force microscopy, immunofluorescence microscopy, quantitative RT-PCR, and a three-dimensional collagen gel contraction assay, we studied the biophysical and structural properties of glomeruli and podocytes in chronic (Tg26 mice [HIV protein expression]) and acute (protamine administration [cytoskeletal rearrangement]) models of podocyte injury. Results Compared with wild-type glomeruli, Tg26 glomeruli became progressively more deformable with disease progression, despite increased collagen content. Tg26 podocytes had disordered cytoskeletons, markedly abnormal focal adhesions, and weaker adhesion; they failed to respond to mechanical signals and exerted minimal traction force in three-dimensional collagen gels. Protamine treatment had similar but milder effects on glomeruli and podocytes. Conclusions Reduced structural integrity of Tg26 podocytes causes increased deformability of glomerular capillaries and limits the ability of capillaries to counter hemodynamic force, possibly leading to further podocyte injury. Loss of normal podocyte mechanical integrity could injure neighboring podocytes due to the absence of normal biophysical signals required for podocyte maintenance. The severe defects in podocyte mechanical behavior in the Tg26 model may explain why Tg26 glomeruli soften progressively, despite increased collagen deposition, and may be the basis for the rapid course of glomerular diseases associated with severe podocyte injury. In milder injury (protamine), similar processes occur but over a longer time. |
| Databáze: | OpenAIRE |
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