Expression of beta 1-integrins on activated mesangial cells in human glomerulonephritis.
beta 1-integrins, a family of cell-surface receptors, mediate cell-matrix interactions that play a critical role in tissue development and tissue remodeling after injury. In this study, to clarify the importance of beta 1-integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of beta 1-integrins, their ligand matrix components, alpha-smooth muscle actin (alpha-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-beta (TGF-beta), and glomerular cellularity in two normal kidneys, ten minimal change nephrotic syndrome, 23 immunoglobulin A (IgA) GN, 13 lupus GN, and four membranous GN kidneys were studied. Immunostaining was performed on frozen sections, using monoclonal anti-alpha-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of alpha 1 beta 1 (collagen/laminin receptor), alpha 5 beta 1 (fibronectin receptor) and TGF-beta. Quantitation of staining indicated that the glomerular expression of alpha 1 beta 1 and alpha 5 beta 1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), alpha-SM actin (P < 0.01), and TGF-beta (P < 0.01). In addition, a correlation was observed between an increased expression of alpha 1 beta 1 and alpha 5 beta 1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing alpha-SM actin strongly expressed alpha 1 beta 1 and alpha 5 beta 1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-beta staining (P < 0.01). In conclusion, enhanced expression of beta 1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-beta appears to be involved in these MC phenotypic changes.
Kuhara
T
T
Department of Pediatrics, School of Medicine, University of Tokushima, Japan.
Kagami
S
S
Kuroda
Y
Y
D000199:Actins / Q000032:analysis; D001685:Biological Factors / Q000032:analysis; D002478:Cells, Cultured; D019084:Fluorescent Antibody Technique, Indirect; D005920:Glomerular Mesangium / Q000166:cytology / Q000473:pathology*; D005921:Glomerulonephritis / Q000473:pathology*; D006801:Humans; D019012:Integrin beta1 / Q000032:analysis*; D016023:Integrins / Q000032:analysis; D008856:Microscopy, Fluorescence; D012016:Reference Values; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000032:analysis*
D000199:Actins; D001685:Biological Factors; D019012:Integrin beta1; D016023:Integrins; D016212:Transforming Growth Factor beta