Biochemical and cellular determinants of renal glomerular elasticity

Addie E. Embry, Hamid Mohammadi, Xinying Niu, Liping Liu, Borren Moe, William A. Miller-Little, Christopher Y. Lu, Leslie A. Bruggeman, Christopher A. McCulloch, Paul A. Janmey, R. Tyler Miller

Research output: Contribution to journalArticle

11 Scopus citations

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 ischemiareperfusion 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.

Original languageEnglish (US)
Article numbere0167924
JournalPloS one
Volume11
Issue number12
DOIs
StatePublished - Dec 2016

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Embry, A. E., Mohammadi, H., Niu, X., Liu, L., Moe, B., Miller-Little, W. A., Lu, C. Y., Bruggeman, L. A., McCulloch, C. A., Janmey, P. A., & Miller, R. T. (2016). Biochemical and cellular determinants of renal glomerular elasticity. PloS one, 11(12), [e0167924]. https://doi.org/10.1371/journal.pone.0167924