Quantitative analyses of osteopontin mRNA expression in human proximal tubules isolated from renal biopsy tissue sections of minimal change nephrotic syndrome and IgA glomerulonephropathy patients.

Osteopontin (OPN), a secreted phosphoprotein and chemotactic to monocytes/macrophages, is upregulated in renal cortical tubules in a variety of rodent models of renal injury and is believed to possibly have a role in tubulointerstitial injury. We previously reported the establishment of a system for the quantification of messenger RNA (mRNA) expression in isolated rat glomeruli using laser-manipulated microdissection and real-time polymerase chain reaction. This system was applied to human renal biopsy specimens. We quantified OPN mRNA expression in proximal tubules of 5 patients with minimal change nephrotic syndrome (MCNS) and 11 patients with mild immunoglobulin A (IgA) glomerulonephritis. We also examined the correlation between OPN mRNA expression in proximal tubules and clinical data and pathological findings in glomeruli and tubulointerstitial regions. Patients with MCNS showed a positive correlation between OPN mRNA expression in proximal tubules and urinary protein excretion (r = 0.93; P < 0.05), whereas for patients with IgA glomerulonephritis, logarithmic values of OPN mRNA expression in proximal tubules positively correlated with low urinary protein levels (r = 0.72; P < 0.05). Pathological changes, ranging from nonexistent to minor, in glomeruli and tubulointerstitium of these patients with mild IgA glomerulonephritis did not significantly correlate with OPN mRNA expression in proximal tubules. In patients with mild IgA glomerulonephritis, OPN mRNA expression in proximal tubules increased exponentially in response to a small amount of urinary protein (<1.2 g/d).