MOLECULAR APPROACHES TO THE STUDY OF RENAL-DISEASE

Recent developments in cell biology and molecular biology have provide d new techniques for molecular studies on renal diseases. The in situ hybridization technique demonstrates the site and the degree of gene e xpression of various cytokines and regulating proteins associated with the altered function of the glomeruli. It is not known, however, if t he expression of these genes is different among various glomerular dis eases. The aim of this study was to elucidate the disease specific phe nomena in glomerular gene expression. Renal biopsy specimens were obta ined from patients with diabetic nephropathy, and IgA nephropathy. The degree of tissue damage as well as the levels of various clinical par ameters were matched between these two groups. In situ hybridization o f mRNA in renal tissues for transforming growth factor (TGF)-beta, sto romelysin (MMP-3) and tissue inhibitor of metalloproteinase (TIMP-1) w ere performed using nonradioactive digoxigenin (DIG)-labelled oligonuc leotide probes. In parallel studies, renal biopsy specimens were stain ed with monoclonal antibody against advanced glycated end-products (AG E). The results demonstrated that the distribution of mRNA expression of TGF-beta was similar between these two diseases, but the expression of MMP-3 and TIMP-1 was parallel with the degree of tissue damage in patients with IgA nephropathy while it was diminished in patients with an advanced degree of tissue damage due to diabetic nephropathy. Posi tive staining of renal tissues with anti-AGE antibody was only observe d in patients with diabetic nephropathy. It is concluded that glycatio n of renal structural proteins might interfere with their metabolism b y enzymes and their inhibitors, while a cytokine responsible for mesan gial expansion was similarly expressed.