TGF-β1 Induces Aberrant Laminin Chain and Collagen Type IV Isotype Expression in the Glomerular Basement Membrane

Abstract

Transforming growth factor-β1 (TGF-β1) contributes to the thickening of the glomerular basement membrane (GBM), abnormal deposition of extracellular matrix (ECM) therein and expansion of the mesangial matrix (MM) in several glomerular kidney diseases. However, the influence of TGF-β1 on the expression of collagen IV isotypes and laminin chains in the GBM and the MM in vivo is not known in detail. By using transgenic mice with TGF-β1 expression targeted to the juxtaglomerular apparatus and a combination of immunohistochemistry, Western blotting, immunoelectron microscopy and in situ hybridization, we investigated the contribution of different laminin chains and collagen type IV isotypes to the basement membrane thickening and mesangial expansion. We report that exposure of the glomerulus to TGF-β1 in vivo induces aberrant deposition of fetal laminin α1, α2 and β1 chains and collagen type IVα1/α2 in the GBM. On the other hand, the TGF-β1-mediated expansion of the mesangial ECM is dominated by the normal components. We found that the cellular origin of at least laminin α1 and α2 chains may be the glomerular endothelial cells. We speculate that the endothelial cells could contribute to TGF-β1-induced glomerulopathy and should be considered as target cells for early intervention in glomerular diseases associated with TGF-β1 in man.