In glomerular epithelial cells (GEC), the actin cytoskeleton is a key determinant of cell morphology and functions, including permselectivity. Complement C5b-9 induces sublytic GEC injury associated with GEC morphological changes and proteinuria. This study addressed the role of Rho GTPases in complement-mediated GEC injury. We demonstrated that the amount of active RhoA increased; while the amount of active Rac1 and Cdc42 were decreased in C5b-9 mediated sublytic GEC injury both in vitro and in glomeruli from rats with PHN in vivo. Complement mediated inactivation of p190RhoGAP may contribute to complement-induced RhoA activation. Overexpression of constitutively active or dominant negative mutants of RhoA, Rac1 and Cdc42 distinctly altered GEC morphology and F-actin pattern. Complement caused changes in GEC actin cytoskeleton, at least in part mediated by a downstream kinase of RhoA--Rho kinase (ROCK). Activation of RhoA exacerbated complement-mediated cytotoxicity in GEC, while inhibition of ROCK attenuated it.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.98529 |
| Date | January 2005 |
| Creators | Zhang, Hui, 1971- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Master of Science (Department of Physiology.) |
| Rights | © Hui Zhang, 2005 |
| Relation | alephsysno: 002328847, proquestno: AAIMR24837, Theses scanned by UMI/ProQuest. |
Page generated in 0.002 seconds