title: Alterations in human glomerular epithelial cells interacting with nonenzymatically glycosylated matrix.
abstract: The glomerular epithelial cells and the glomerular basement membrane are important constituents of the permselective barrier in the kidney. These are affected in diabetic nephropathy, one of the long-term complications in diabetic patients. Nonenzymatic glycosylation resulting in the accumulation of advanced glycosylation end products correlates with the development of long-term complications in diabetes. The interaction of cells with extracellular matrix proteins plays a critical role in a variety of biological processes. Recent studies show that cell-matrix interactions mediated by integrins can transduce biochemical signals to the cell interior and regulate cell behavior. In this paper we demonstrate that interactions of human glomerular epithelial cells with a nonenzymatically glycated matrix are altered with defective cell spreading, reduced phosphorylation of focal adhesion kinase and reduced activity of mitogen-activated protein kinase. These data suggest that matrix glycation interferes with normal cell-matrix interactions and intracellular signaling that can potentially result in differential gene expression contributing to the changes seen in diabetic nephropathy.
authors.affiliation: Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota 55455, USA. kris0019@maroon.tc.umn.edu
authors.forename: U
authors.initials: U
authors.lastname: Krishnamurti
authors.forename: E
authors.initials: E
authors.lastname: Rondeau
authors.forename: J D
authors.initials: JD
authors.lastname: Sraer
authors.forename: A F
authors.initials: AF
authors.lastname: Michael
authors.forename: E C
authors.initials: EC
authors.lastname: Tsilibary
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002461:Cell Line, Transformed; D002465:Cell Movement; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology; D004847:Epithelial Cells / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006031:Glycosylation; D006801:Humans; D007678:Kidney Glomerulus / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human