DIFFERENTIAL EXPRESSION OF TRANSFORMING GROWTH-FACTOR-BETA ISOFORMS AND RECEPTORS IN EXPERIMENTAL MEMBRANOUS NEPHROPATHY

In membranous nephropathy (MN) overproduction of matrix by glomerular epithelial cells (GEC) is believed to be responsible for glomerular ba sement membrane thickening and spikes. We studied experimental MN in r ats (passive Heymann nephritis, PHN) at 5, 10 and 30 days. PHN rats ex hibited a marked increase in GEC immunostaining for TGF-beta 2 at all time points. TGF-beta 3 staining was increased at day 10 only, and TGF -beta 1 was unchanged. Glomerular mRNA for TGF-beta 2 and -beta 3 was increased by day when urine protein increased, whereas TGF-beta 1 was not. TGF-beta 2 bioactivity was increased at day 5. There was also a m arked increase in GEC immunostaining for TGF-beta receptor type I (T b eta IR) and TGF-beta receptor type II (T beta IIR) at all time points in PHN. mRNA levels for both receptors increased at day 5. Increases i n protein expression and mRNA levels for the TGF-beta 2 and -beta 3 is oforms, and T beta IR and T beta RII were prevented by complement depl etion. We conclude that complement-mediated injury to the GEC in vivo is associated with the up-regulation of TGF-beta 2 and -beta 3 isoform s, an increase in TGF-beta 2 bioactivity,and an increase in T beta RI and T beta RII expression. This contrasts with changes in TGF-beta 1 r eported in mesangial disease, suggesting that TGF-beta 2 and -beta 3 m ay be important in diseases of the GEC. The differential expression of TGF-beta isoforms and receptors map be important determinants of the GEC response to injury.