Syndecan‐4 up‐regulation in proliferative renal disease is related to microfilament organization

Syndecan‐4 is a transmembrane heparan sulfate proteoglycan (HSPG) expressed widely in mammalian cells. It has been implicated in growth‐factor binding, cell‐extracellular matrix adhesion, and tissue damage responses. Although several HSPGs are present within kidney mesangium and glomerular basement membranes, no data are available on the synthesis of syndecan‐4 by mesangial cells or its expression in human renal disease. We examined renal biopsy specimens from normal controls, nonproliferative disease (thin‐membrane disease), and progressive proliferative disease (IgA nephropathy). By using RT‐PCR and immunohistochemical staining, we identified an increase in both gene expression (IgA nephropathy vs. thin membrane disease, P = 0.0004) and synthesis of syndecan‐4 in progressive proliferative disease. Syndecan‐4 increased within both mesangium and tubulo‐interstitium, as did α‐actinin, a microfilament cytoskeletal component. Syndecan‐4 was a focal adhesion component in human mesangial cells, colocalizing with vinculin and α‐actinin, and was present in the cortical, submembraneous myosin sheath as seen for α‐actinin. Both syndecan‐4 and α‐actinin were retained selectively in detergent‐resistant cytoskeleton‐matrix preparations, emphasizing their close association in cell‐matrix adhesion. Syndecan‐4 may be important in the adhesion, migration, and proliferation of HMC, and its up‐regulation could indicate proliferative disease.