TGF-beta1 induces aberrant laminin chain and collagen type IV isotype expression in the glomerular basement membrane. 2003

Qing Chai, and Søren Krag, and Jeffrey H Miner, and Jens Randel Nyengaard, and Song Chai, and Lise Wogensen
Research Laboratory for Biochemical Pathology, Institute for Experimental Clinical Research, Aarhus Kommunehospital, Aarhus, Denmark.

Transforming growth factor-beta1 (TGF-beta1) 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-beta1 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-beta1 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-beta1 in vivo induces aberrant deposition of fetal laminin alpha1, alpha2 and beta1 chains and collagen type IValpha1/alpha2 in the GBM. On the other hand, the TGF-beta1-mediated expansion of the mesangial ECM is dominated by the normal components. We found that the cellular origin of at least laminin alpha1 and alpha2 chains may be the glomerular endothelial cells. We speculate that the endothelial cells could contribute to TGF-beta1-induced glomerulopathy and should be considered as target cells for early intervention in glomerular diseases associated with TGF-beta1 in man.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007678 Kidney Glomerulus A cluster of convoluted capillaries beginning at each nephric tubule in the kidney and held together by connective tissue. Glomerulus, Kidney
D007797 Laminin Large, noncollagenous glycoprotein with antigenic properties. It is localized in the basement membrane lamina lucida and functions to bind epithelial cells to the basement membrane. Evidence suggests that the protein plays a role in tumor invasion. Merosin,Glycoprotein GP-2,Laminin M,Laminin M Chain,Chain, Laminin M,Glycoprotein GP 2,M Chain, Laminin
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D005260 Female Females
D005786 Gene Expression Regulation Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation. Gene Action Regulation,Regulation of Gene Expression,Expression Regulation, Gene,Regulation, Gene Action,Regulation, Gene Expression
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D001485 Basement Membrane A darkly stained mat-like EXTRACELLULAR MATRIX (ECM) that separates cell layers, such as EPITHELIUM from ENDOTHELIUM or a layer of CONNECTIVE TISSUE. The ECM layer that supports an overlying EPITHELIUM or ENDOTHELIUM is called basal lamina. Basement membrane (BM) can be formed by the fusion of either two adjacent basal laminae or a basal lamina with an adjacent reticular lamina of connective tissue. BM, composed mainly of TYPE IV COLLAGEN; glycoprotein LAMININ; and PROTEOGLYCAN, provides barriers as well as channels between interacting cell layers. Basal Lamina,Basement Lamina,Lamina Densa,Lamina Lucida,Lamina Reticularis,Basement Membranes,Densas, Lamina,Lamina, Basal,Lamina, Basement,Lucida, Lamina,Membrane, Basement,Membranes, Basement,Reticularis, Lamina

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