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Alpha8 integrin in glomerular mesangial cells and in experimental glomerulonephritis
A Hartner1, H Schöcklmann, F Pröls
1Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany.
Kidney International
|October 3, 1999
Summary
Alpha-8 integrin is found in mesangial cells (MCs) of the glomerulus. Its expression changes during kidney injury and is regulated by TGF-beta1, suggesting a role in glomerular disease.
Area of Science:
- Nephrology
- Cell Biology
- Integrin Signaling
Background:
- Mesangial cell (MC) proliferation and extracellular matrix accumulation are key to glomerular injury.
- Beta1 integrins mediate MC responses to extracellular matrix components.
- Alpha-8 integrin (alpha8) is newly identified in glomeruli and renal vasculature.
Purpose of the Study:
- Investigate glomerular expression of alpha-8 integrin in mouse, rat, and human kidneys.
- Examine alpha-8 regulation in cultured MCs and in nephritic rats.
Main Methods:
- Immunohistochemistry, immunocytochemistry, and Western blotting for alpha-8 protein.
- Northern blot analysis for alpha-8 mRNA regulation by TGF-beta1.
- In vivo studies in anti-Thy1.1 nephritis rat model.
Main Results:
- Alpha-8 integrin is strongly expressed in MCs of human, rat, and mouse glomeruli.
- Glomerular alpha-8 abundance changes during anti-Thy1.1 nephritis, increasing with MC proliferation.
- Cultured MCs organize alpha-8 into focal contacts on fibronectin/vitronectin; TGF-beta1 increases alpha-8 expression.
Conclusions:
- Alpha-8 integrin is exclusively expressed in glomerular MCs across species.
- Alpha-8 gene and protein expression are regulated in MCs in vitro and in vivo.
- Alpha-8beta1 integrin may play a significant role in MC matrix interactions and glomerular pathophysiology.