GLOMERULAR TRANSFORMING GROWTH-FACTOR-BETA-1 MESSENGER-RNA AS A MARKER OF GLOMERULOSCLEROSIS - APPLICATION IN RENAL BIOPSIES

As transforming growth factor-beta 1 (TGF-beta 1) is implicated in the pathogenesis of glomerulosclerosis, the aim of the study was to demon strate if levels of glomerular TGF-beta 1 mRNA in renal biopsies corre lated with glomerulosclerosis. Glomeruli were collected by microdissec tion from renal biopsies in patients with membranous nephropathy, lupu s nephritis, diabetic nephropathy, minimal change disease and IgA neph ropathy presented by proteinuria when serum creatinine was <3 mg%. Glo merular mRNAs were reverse transcribed and TGF-beta 1, alpha 2(IV) col lagen, beta-actin cDNA quantitated by competitive polymerase chain rea ction (PCR). By semiquantitative electron microscopy, a 3.5-fold incre ase of glomerular TGF-beta 1/beta-actin mRNA ratio in the moderate scl erotic group (n = 23, p < 0.01) and a 1.5-fold increase in the mild sc lerotic group (n = 22, p < 0.05) were observed when compared to the mi nimal sclerotic group (n = 12). A concordant increase of glomerular al pha 2(IV) collagen mRNA was found with 2.2- and 1.3-fold in moderate a nd mild sclerotic groups, respectively. The TGF-beta 1/beta-actin mRNA ratios were highest in membranous nephropathy (466.4 +/- 133.4, n = 1 1), followed by lupus nephritis (394.9 +/- 94.8, n = 12) and diabetic nephropathy (333.2 +/- 97.6, n = 10). Patients with minimal change dis ease (233.1 +/- 54.1, n = 15) and IgA nephropathy (185.3 +/- 39.6, n = 9) had low levels. The degree of glomerulosclerosis in each group fol lowed the TGF-beta 1/beta-actin mRNA ratios indicating that the level is the major determinant of glomerulosclerosis but not the disease ent ities. Glomerular TGF-beta 1/beta-actin mRNA ratio did not correlate w ith clinical parameters such as the urinary protein excretion and crea tinine clearance. These results suggest that glomerular TGF-beta 1/bet a-actin mRNA ratio may be used as a marker of glomerulosclerosis in re nal biopsy to reflect the local sclerotic process.