Integrin-linked kinase in renal disease: connecting cell-matrix interaction to the cytoskeleton

被引:39
作者
Blattner, SM [1 ]
Kretzler, M [1 ]
机构
[1] Univ Munich, Nephrol Ctr, D-80336 Munich, Germany
关键词
beta-catenin; epithelial mesenchymal transition; glomerulus; podocyte; tubulo-interstitial fibrosis;
D O I
10.1097/01.mnh.0000172730.67746.5b
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose of review Cellular functions like proliferation, differentiation, migration, morphogenesis and apoptosis are modulated by the extracellular matrix. Integrins are the prototypic heterodimeric transmembrane matrix receptors with competing affinities for individual extracellular matrix ligands. The intracellular integrin domain clusters cytoplasmic proteins into focal adhesion plaques for bidirectional (outside-in and inside-out) signalling. Integrin-linked kinase organizes the connections of the extracellular matrix via integrins to the cytoskeleton and is involved in adhesion plaque signalling. In this review, an introduction of integrin-linked kinase structure and function is followed by a summary of our current understanding of integrin-linked kinase in renal disease with special focus on glomerular, cell-matrix interaction. Recent findings Differential regulation of integrin-linked kinase has been observed during the pathogenesis of glomerular disease and tubulo-interstitial fibrosis. In outside-in signalling integrin-linked kinase mediates the response of renal cells to alterations in matrix and growth factor environments. Inside-out signalling transduces inflammatory and oxidative stress responses into decreased matrix attachment. Downstream signalling of integrin-linked kinase activates the Writ pathway with a switch towards a proliferative, mesenchymal phenotype. In concert with interacting molecules integrinl linked kinase influences the actin cytoskeleton, resulting in shape change and focal adhesion dysfunction observed in podocyte failure and tubulo-interstitial fibrosis. Summary Integrin-linked kinase has emerged as a key player at the interface between extracellular matrix, integrins, actin-based cytoskeleton and cellular phenotype in kidney diseases. Future studies focusing on interacting molecules and modification of integrin-linked kinase function in vivo will better define the role of cell matrix signalling in progressive renal failure.
引用
收藏
页码:404 / 410
页数:7
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