Hemopexin induces nephrin-dependent reorganization of the actin cytoskeleton in podocytes

Rachel Lennon, Anurag Singh, Gavin I Welsh, Richard J Coward, Simon Satchell, Lan Ni, Peter W Mathieson, Winston W Bakker, Moin A Saleem

Research output: Contribution to journalArticle (Academic Journal)

81 Citations (Scopus)

Abstract

Hemopexin is an abundant plasma protein that effectively scavenges heme. When infused into rats, hemopexin induces reversible proteinuria, and activated hemopexin is increased in children with minimal change nephrotic syndrome. These observations suggest a role for hemopexin in glomerular disease; in this study, the effects of active hemopexin on human podocytes and glomerular endothelial cells, the two cell types that compose the glomerular filtration barrier, were investigated. Within 30 min of treatment with hemopexin, actin reorganized from stress fibers to cytoplasmic aggregates and membrane ruffles in wild-type podocytes. This did not occur in nephrin-deficient podocytes unless they were transfected with nephrin-expressing plasmids. Furthermore, hemopexin did not affect actin organization in cells that do not express nephrin, specifically human glomerular endothelial cells, fibroblasts, and HEK293 cells. The effects of hemopexin on wild-type podocytes reversed within 4 h and were inhibited by preincubation with human plasma. Treatment with hemopexin activated protein kinase B in both wild-type and nephrin-deficient podocytes but activated RhoA only in wild-type cells. In addition, hemopexin led to a selective increase in the passage of albumin across monolayers of glomerular endothelial cells and to a reduction in glycocalyx. In summary, active hemopexin causes nephrin-dependent remodeling of podocytes and affects permeability of the glomerular filtration barrier by degrading the glycocalyx.

Original languageEnglish
Pages (from-to)2140 - 2149
Number of pages10
JournalJournal of the American Society of Nephrology
Volume19
Issue number11
DOIs
Publication statusPublished - Nov 2008

Keywords

  • Actins
  • Base Sequence
  • Cell Line
  • Cell Membrane Permeability
  • Cytoskeleton
  • Endothelial Cells
  • Glycocalyx
  • Green Fluorescent Proteins
  • Hemopexin
  • Humans
  • Kidney Glomerulus
  • Membrane Proteins
  • Podocytes
  • Proto-Oncogene Proteins c-akt
  • RNA, Small Interfering
  • Recombinant Proteins
  • Transfection
  • rhoA GTP-Binding Protein

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