Expression of β1-integrins on activated mesangial cells in human glomerulonephritis

Abstract

β1-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 β1- integrins in human glomerulonephritis (GN), the relationship among the glomerular expression of β1-integrins, their ligand matrix components, α- smooth muscle actin (α-SM actin) as a marker of activated mesangial cells (MC), transforming growth factor-β (TGF-β), 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-α-SM actin antibody and polyclonal antibodies against fibronectin, collagen type IV, laminin, each subunit of α1β1 (collagen/laminin receptor), α5β1 (fibronectin receptor) and TGF-β. Quantitation of staining indicated that the glomerular expression of α1β1 and α5β1 integrins correlated with the mesangial amounts of their ligands, collagen type IV, laminin and fibronectin (P < 0.01), α-SM actin (P < 0.01), and TGF-β (P < 0.01). In addition, a correlation was observed between an increased expression of α1β1 and α5β1 integrins and the degree of glomerular cell proliferation (P < 0.01). Double immunostaining showed that activated MC expressing α-SM actin strongly expressed α1β1 and α5β1 integrins, and these MC phenotypic alterations paralleled the level of glomerular TGF-β staining (P < 0.01). In conclusion, enhanced expression of β1-integrins by activated MC may contribute to the pathological mesangial remodeling characterized by MC proliferation and matrix deposition in human GN. Increased glomerular TGF-β appears to be involved in these MC phenotypic changes.