title: ERK1/2 mediates cytoskeleton and focal adhesion impairment in proximal epithelial cells after renal ischemia.
abstract: ERK1/2 has been reported to be activated in the postischemic kidney but its precise role in ischemia/reperfusion (I/R) injury remains unclear. Therefore, we have studied the expression of ERK1/2 and its contribution to cytoskeleton organization and cell adhesion structures in proximal tubular cells, all affected during I/R. We observe ERK1/2 activation at 24 hours of reperfusion in an in vivo model of I/R, when acute tubular necrosis (ATN) is most prominent. In addition, by means of an in vitro model of hypoxia/reoxygenation (H/R) in rat proximal NRK-52E cells we show that p-ERK1/2 is strongly induced early during reoxygenation. Moreover, we also demonstrate that ROS generation contributed to this induction. ERK1/2 activation is contemporary with cell-cell adhesion disruption during reoxygenation but the use of U0126 did not have effect on adherens junctions (AJ) and tight junctions (TJ) disassembly, neither on epithelial monolayer permeability. On the contrary, ERK1/2 affects cytoskeleton organization and focal complexes assembly during H/R, since U0126 improved actin and tubulin cytoskeleton structure, reduced cell contraction and prevented paxillin redistribution. In summary, ERK1/2 signalling plays an essential role in I/R induced injury, mediating proximal cell adhesive alterations which lead to tubular damage and ultimately might compromise renal function.
authors.affiliation: Department of Pathology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sáenz-Morales
authors.forename: Elisa
authors.initials: E
authors.lastname: Conde
authors.forename: María M
authors.initials: MM
authors.lastname: Escribese
authors.forename: María
authors.initials: M
authors.lastname: García-Martos
authors.forename: Laura
authors.initials: L
authors.lastname: Alegre
authors.forename: Ignacio
authors.initials: I
authors.lastname: Blanco-Sánchez
authors.forename: María Laura
authors.initials: ML
authors.lastname: García-Bermejo
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000648:ultrastructure*; D004847:Epithelial Cells / Q000201:enzymology / Q000648:ultrastructure; D022001:Focal Adhesions / Q000648:ultrastructure*; D000860:Hypoxia / Q000503:physiopathology; D007511:Ischemia / Q000201:enzymology* / Q000473:pathology; D007668:Kidney / Q000098:blood supply*; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000648:ultrastructure; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3