ERK1/2 mediates cytoskeleton and focal adhesion impairment in proximal epithelial cells after renal ischemia.
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.
Sáenz-Morales
David
D
Department of Pathology, Hospital Universitario Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain.
Conde
Elisa
E
Escribese
María M
MM
García-Martos
María
M
Alegre
Laura
L
Blanco-Sánchez
Ignacio
I
García-Bermejo
María Laura
ML
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
D017382:Reactive Oxygen Species; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3