Abstract
Glomerulosclerosis is the final event of many chronic renal diseases. It is characterized by the accumulation of extracellular matrix (ECM) proteins. Collagen IV is one of the major ECM proteins that accumulate in glomeruli in chronic renal disease. Lysyl oxidase (LOX) -induced cross-linking of collagen may be involved in these processes. Therefore, we studied LOX mRNA expression by reverse transcriptase-polymerase chain reaction (RT-PCR) in progressive proliferative glomerulonephritis (anti-Thy 1.1 nephritis induced in unilaterally nephrectomized rats) and reversible proliferative glomerulonephritis (anti-Thy 1.1 nephritis induced in normal rats) . Segmental glomerulosclerosis was observed in about 10% of glomeruli in rats with anti-Thy 1.1 nephritis induced in unilateral nephrectomy at eight weeks after disease induction. A marked increase in glomerular LOX mRNA expression was also demonstrated. In contrast, the glomerulus at 7 days after anti-Thy 1.1 nephritis induced in normal unmanipulated rats was characterized by marked glomerular cell proliferation and matrix expansion. However, there was no evidence of sclerosis in the glomerulus in this model and there was no LOX mRNA expression in glomeruli. These results suggest that expression of LOX in glomeruli may be a marker for the occurrence of glomerulosclerosis, and that LOX may also play a key role in the development of irreversible glomerular fibrosis by cross-linking of collagen fibrils.
