Distribution of extracellular matrix receptors in various forms of glomerulonephritis

Abstract

Integrins are heterodimeric transmembrane receptor glycoproteins consisting of α and β subunits that mediate adhesion and interactions between cells and extracellular matrix. Such interactions may be perturbed in various pathologic states, resulting in the altered phenotypic expressions of the integrins in affected tissues. To ascertain the alterations in integrins in various renal diseases, their distribution was investigated in different forms of glomerulonephritis by indirect immunofluorescence and immunoelectron microscopy using specific antibodies directed against β 1 integrins and integrin α v β 3 (vitronectin receptor). In addition, the distribution of certain extracellular matrix components (ie, fibronectin, vitronectin, and type IV collagen) was examined. Integrin β 1 and α v β 3 were highly expressed in proliferating mesangial cells in immunoglobulin A nephropathy, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. Their putative ligands (ie, fibronectin, vitronectin, and type IV collagen) also were increased in the expanded mesangial regions. In immunoglobulin A nephropathy, integrin β 1 and α v β 3 were seen by immunoelectron microscopy to be localized to the mesangial cell membranes in close proximity to the immune complex deposits; however, fibronectin and vitronectin immunoreactivities were observed in the mesangial immune complex deposits. Similarly, vitronectin also was detected in the immune complex deposits of other forms of proliferative nephritis, ie, membranoproliferative glomerulonephritis type I and diffuse proliferative lupus nephritis. In diffuse proliferative lupus nephritis, the cellular crescents displayed immunoreactivity toward integrin α v β 3 and vitronectin. In nonimmune complex glomerular disease associated with nephrotic syndrome (ie, minimal change nephrotic syndrome), integrin α 3 β 1, which normally has a linear capillary distribution, was decreased. In immune complex nephritis associated with nephrotic syndrome (ie, membranous nephropathy), integrin α 3 β 1 immunoreactivity was focally disrupted and capillary loops displayed a discontinuous linear distribution. Finally, in membranous nephropathy, immunoreactivity toward vitronectin was accentuated in immune complex deposits. The differential altered distributions of the integrins and of their ligands may be reflective of mesangial cell proliferative activity in certain forms of glomerulonephritis, while in other forms of glomerular diseases, the decreased immunoreactivity of integrin α 3 β 1 may be related to the glomerular capillary wall alterations associated with proteinuric states.