Korean J Nephrol.  2000 Sep;19(5):857-867.

Mechanism of Glomerular Basement Membrane Thickening in Human Membranous Nephropathy

• Kim JY
• Kim TS
• Hong HK
• Lee HS

Abstract

Membranous nephropathy is the most common cause of nephrotic syndrome in adult. To investigate the molecular mechanisms which underlie thickening of glomerular basement membrane, we analyzed alpha1(IV) collagen, alpha4(IV) collagen, laminin A, laminin B1, laminin B2, s-laminin, fibronectin, TGF-beta1 and TGF-beta2 mRNA expression in 21 renal biopsies with membranous nephropathy using in situ hybridization. In addition, 7 renal biopsies with no detectable abnormalities were used as control. In membranous nephropathy, the numbers of glomerular visceral epithelial cells expressing alpha1(IV) collagen, alpha4(IV) collagen, s-laminin and TGF-beta1 mRNA were significantly larger than in controls(p<0.05). Laminin A, laminin B1, laminin B2, fibronectin, and TGF-beta2 mRNA were rarely expressed in membranous nephropathy and in control group. The number of TGFbeta-1 mRNA expressing cells/glomerular cross-section correlated to that of alpha1(IV) collagen mRNA expressing cells (p< 0.05). These results indicate that increased presence of glomerular basement membrane proteins in spikes of membranous nephropathy is associated with enhanced mRNA expression of those proteins in the glomerular visceral epithelial cells. Subepithelial deposits in membranous nephropathy stimulate glomerular visceral epithelial cells to produce TGF-beta1, which in turn could mediate the expression of glomerular basement membrane protein genes by glomerular visceral epithelial cells.

Keyword

Membranous nephropathy; In situ hybridization; alpha1(IV) collagen; alpha4 (IV) collagen; S-laminin; TGF-beta1

MeSH Terms

Adult
Biopsy
Collagen
Collagen Type IV
Fibronectins
Glomerular Basement Membrane*
Glomerulonephritis, Membranous*
Humans*
In Situ Hybridization
Laminin
Nephrotic Syndrome
Podocytes
RNA, Messenger
Transforming Growth Factor beta1
Transforming Growth Factor beta2
Collagen
Collagen Type IV
Fibronectins
Laminin
RNA, Messenger
Transforming Growth Factor beta1
Transforming Growth Factor beta2