mRNA expression of glomerular basement membrane proteins and TGF- ? 1 in human membranous nephropathy

✍ Scribed by Kim, Tae Sook; Kim, Jung Yeon; Hong, Hye Kyoung; Lee, Hyun Soon

• Publisher: John Wiley and Sons
• Year: 1999
• Tongue: English
• Weight: 416 KB
• Volume: 189
• Category: Article
• ISSN: 0022-3417
• DOI: 10.1002/(sici)1096-9896(199911)189:3<425::aid-path454>3.0.co;2-6

✦ Synopsis

Immunogold densities for the 'classical' and 'novel' chains of type IV collagen, laminin, and fibronectin are increased in the spikes in human membranous nephropathy (MN). To investigate the molecular mechanisms which underlie these changes in glomerular basement membrane (GBM) components, 1(IV) collagen, 4(IV) collagen, S-laminin, fibronectin, transforming growth factor (TGF)-1 and TGF-2 mRNA expression was examined in 12 renal biopsy specimens with MN and six renal biopsies with no detectable abnormality by RNA in situ hybridization. In controls, there were relatively low signals of 1(IV) collagen, 4(IV) collagen, S-laminin, and TGF-1 mRNAs, but there were no fibronectin or TGF-2 transcripts in glomerular cells. In MN, the number of 4(IV) collagen, 1(IV) collagen, S-laminin or TGF-1 mRNA-expressing cells per glomerular cross-section was significantly larger than in controls (p<0•05), and fibronectin mRNA was occasionally expressed in glomerular visceral epithelial cells (GECs). No message for TGF-2 was seen in MN. The number of TGF-1 mRNA-expressing cells per glomerular cross-section significantly correlated with that of 1(IV) mRNA-expressing cells (p<0•01). The MN patients with positivie signal for fibronectin mRNA exhibited more severe GBM thickening than those without (p<0•05). These results indicate that the increased presence of GBM proteins in spikes of MN is associated with enhanced mRNA expression of these proteins. They also suggest that subepithelial deposits in MN stimulate GECs to produce TGF-1, which in turn could mediate the expression of GBM protein genes by GECs.