title: Biochemical and Cellular Determinants of Renal Glomerular Elasticity.
abstract: The elastic properties of renal glomeruli and their capillaries permit them to maintain structural integrity in the presence of variable hemodynamic forces. Measured by micro-indentation, glomeruli have an elastic modulus (E, Young's modulus) of 2.1 kPa, and estimates from glomerular perfusion studies suggest that the E of glomeruli is between 2 and 4 kPa. F-actin depolymerization by latrunculin, inhibition of acto-myosin contractility by blebbistatin, reduction in ATP synthesis, and reduction of the affinity of adhesion proteins by EDTA reduced the glomerular E to 1.26, 1.7, 1.5, and 1.43 kPa, respectively. Actin filament stabilization with jasplakinolide and increasing integrin affinity with Mg2+ increased E to 2.65 and 2.87 kPa, respectively. Alterations in glomerular E are reflected in commensurate changes in F/G actin ratios. Disruption of vimentin intermediate filaments by withaferin A reduced E to 0.92 kPa. The E of decellularized glomeruli was 0.74 kPa, indicating that cellular components of glomeruli have dominant effects on their elasticity. The E of glomerular basement membranes measured by magnetic bead displacement was 2.4 kPa. Podocytes and mesangial cells grown on substrates with E values between 3 and 5 kPa had actin fibers and focal adhesions resembling those of podocytes in vivo. Renal ischemia and ischemia-reperfusion reduced the E of glomeruli to 1.58 kPa. These results show that the E of glomeruli is between 2 and 4 kPa. E of the GBM, 2.4 kPa, is consistent with this value, and is supported by the behavior of podocytes and mesangial cells grown on variable stiffness matrices. The podocyte cytoskeleton contributes the major component to the overall E of glomeruli, and a normal E requires ATP synthesis. The reduction in glomerular E following ischemia and in other diseases indicates that reduced glomerular E is a common feature of many forms of glomerular injury and indicative of an abnormal podocyte cytoskeleton.
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: Addie E
authors.initials: AE
authors.lastname: Embry
authors.affiliation: Center for Matrix Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Hamid
authors.initials: H
authors.lastname: Mohammadi
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: Xinying
authors.initials: X
authors.lastname: Niu
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: Liping
authors.initials: L
authors.lastname: Liu
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: Borren
authors.initials: B
authors.lastname: Moe
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: William A
authors.initials: WA
authors.lastname: Miller-Little
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.
authors.forename: Christopher Y
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Nephrology, MetroHealth Medical Center, Case-Western Reserve University, Cleveland, Ohio, United States of America.
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Bruggeman
authors.affiliation: Center for Matrix Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Christopher A
authors.initials: CA
authors.lastname: McCulloch
authors.affiliation: Physiology and Biophysics, Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Janmey
authors.affiliation: Nephrology and Medicine, U.T. Southwestern Medical School, Dallas, Texas, United States of America.|Medicine, Dallas VAMC, Dallas, Texas, United States of America.
authors.forename: R Tyler
authors.initials: RT
authors.lastname: Miller
mesh_terms: D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002460:Cell Line; D055119:Elastic Modulus; D016023:Integrins / Q000378:metabolism; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D050527:Mesangial Cells / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D050199:Podocytes / Q000378:metabolism; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D016023:Integrins; D053778:Thiazolidines; D000255:Adenosine Triphosphate; C037067:latrunculin A