IMMUNOHISTOCHEMICAL LOCALIZATION OF LATENT TRANSFORMING-GROWTH-FACTOR-BETA BINDING-PROTEIN IN IGA NEPHROPATHY

It has been demonstrated that cultured mesangial cells (MC) express la tent transforming growth factor (TGF)-beta binding protein (LTBP) mRNA , and that LTBP might he essential for the extracellular matrix (ECM) accumulation stimulated by TGF-beta in cultured MC. We performed a stu dy to test the pathophysiological role of LTBP in mesangial ECM accumu lation in human glomerulonephropathies. The expression of LTBP in 64 r enal biopsies of patients with renal diseases was examined by immunohi stochemical staining with the specific antibody raised against human L TBP. The biopsy specimens were divided into three groups: Group 1, IgA nephropathy; Group 2, IgA negative mesangial proliferative glomerulon ephritis, which mainly consisted of diabetic nephropathy and lupus nep hritis; and Group 3, non-proliferative nephropathy, which consisted of minimal change and membranous nephropathy. Immunohistochemical staini ng of LTBP was significantly detected in mesangial/paramesangial area of glomerulus in Group 1, but not observed in Group 2 or Group 3. The intensity of staining was well related to the grade of mesangial ECM a ccumulation in Group 1. These findings suggest that the LTBP-TGF-beta complex may play a pivotal role in ECM accumulation in IgA nephropathy , and that modification of LTBP-ECM interaction might provide a new th erapeutic strategy against the progression of glomerulosclerosis.