TY - JOUR
T1 - α8 integrin in glomerular mesangial cells and in experimental glomerulonephritis
AU - Hartner, Andrea
AU - Schöckliviann, Harald
AU - Pröls, Felicitas
AU - Müller, Ulrich
AU - Bernd Sterzel, R.
N1 - Funding Information:
Support for this study was provided by the Deutsche Forschungsgemeinschaft, Sonderforschungsbereich 263/B5 and Klinische Forschergruppe, Ste196/3–1. We acknowledge the expert technical assistance of Mr. Hans Fees, Ms. Susanne Arnold, Ms. Elisabeth Weichmann and Ms. Elke Pausch.
PY - 1999
Y1 - 1999
N2 - Background. Mesangial cell (MC) proliferation and extracellular matrix accumulation are typical responses of renal glomeruli to injury. Extracellular matrix components are known to affect MC behavior, which is mediated primarily via integrin receptors of the β1 family. In addition to α1, α3, α5, and α6 chains of β1 integrins, recent studies have shown the α8 chain to be expressed in glomeruli and renal vasculature. α8β1 can serve as a receptor for fibronectin, which is abundant in the mesangium. We investigated the glomerular expression pattern of the α8 chain in renal tissues of mouse, rat, and humans as well as in cultured MCs. In addition, the regulation of α8 expression in MCs was studied in culture and in nephritic rats. Methods. The expression of α8 protein in kidney tissue and cultured MCs was investigated by immunohistochemistry, immunocytochemistry, and Western blotting. The effects of TGF-β1 on α8 mRNA levels in MCs were studied by Northern blot analysis. In addition, time course studies of glomerular abundance and localization of α8 were performed in rats with mesangioproliferative anti-Thv1.1 nephritis. Results. In tissue sections of normal human, rat, and mouse kidney, we found strong immunohistochemical staining for α8 in the mesangium and in the media of renal arterioles. Double staining for α8 and Thv1.1, a surface antigen of rat MCs, showed α8 to be specifically expressed in MCs but not in glomerular endothelial and epithelial cells. In anti-Thv1.1 nephritis of rats, the glomerular abundance of α8 protein was reduced in the early mesangiolytic phase but was increased greatly with subsequent MC proliferation, peaking at day 6 of disease. At later stages of this reversible form of nephritis, the number of MCs and the extent mesangial α8 staining declined to control levels. Cell culture experiments revealed that freshly plated MCs organize α8 into focal contacts within one hour after attachment to fibronectin and vitronectin substrata, showing colocalization with focal contact proteins vinculin and talin. Stimulation of MCs with transforming growth factor-β1 led to increases of α8 mRNA and protein levels. Conclusions. These results show that in human, rat; and mouse glomeruli, α8 integrin is strongly and exclusively expressed in MCs. Gene expression of α8 is regulated in cultured MCs, and α8 protein abundance is regulated in vivo and in MC culture. It is currently unclear what functional properties this integrin receptor protein has with regard to MC anchorage to extracellular matrix and modulation of the MC phenotype in normal and diseased glomeruli. However, in view of its abundance in the mesangium, α8β1 integrin could be an important MC receptor of matrix ligands and may play a role in the embryology, physiology, and pathophysiology of the glomerular capillary tuft.
AB - Background. Mesangial cell (MC) proliferation and extracellular matrix accumulation are typical responses of renal glomeruli to injury. Extracellular matrix components are known to affect MC behavior, which is mediated primarily via integrin receptors of the β1 family. In addition to α1, α3, α5, and α6 chains of β1 integrins, recent studies have shown the α8 chain to be expressed in glomeruli and renal vasculature. α8β1 can serve as a receptor for fibronectin, which is abundant in the mesangium. We investigated the glomerular expression pattern of the α8 chain in renal tissues of mouse, rat, and humans as well as in cultured MCs. In addition, the regulation of α8 expression in MCs was studied in culture and in nephritic rats. Methods. The expression of α8 protein in kidney tissue and cultured MCs was investigated by immunohistochemistry, immunocytochemistry, and Western blotting. The effects of TGF-β1 on α8 mRNA levels in MCs were studied by Northern blot analysis. In addition, time course studies of glomerular abundance and localization of α8 were performed in rats with mesangioproliferative anti-Thv1.1 nephritis. Results. In tissue sections of normal human, rat, and mouse kidney, we found strong immunohistochemical staining for α8 in the mesangium and in the media of renal arterioles. Double staining for α8 and Thv1.1, a surface antigen of rat MCs, showed α8 to be specifically expressed in MCs but not in glomerular endothelial and epithelial cells. In anti-Thv1.1 nephritis of rats, the glomerular abundance of α8 protein was reduced in the early mesangiolytic phase but was increased greatly with subsequent MC proliferation, peaking at day 6 of disease. At later stages of this reversible form of nephritis, the number of MCs and the extent mesangial α8 staining declined to control levels. Cell culture experiments revealed that freshly plated MCs organize α8 into focal contacts within one hour after attachment to fibronectin and vitronectin substrata, showing colocalization with focal contact proteins vinculin and talin. Stimulation of MCs with transforming growth factor-β1 led to increases of α8 mRNA and protein levels. Conclusions. These results show that in human, rat; and mouse glomeruli, α8 integrin is strongly and exclusively expressed in MCs. Gene expression of α8 is regulated in cultured MCs, and α8 protein abundance is regulated in vivo and in MC culture. It is currently unclear what functional properties this integrin receptor protein has with regard to MC anchorage to extracellular matrix and modulation of the MC phenotype in normal and diseased glomeruli. However, in view of its abundance in the mesangium, α8β1 integrin could be an important MC receptor of matrix ligands and may play a role in the embryology, physiology, and pathophysiology of the glomerular capillary tuft.
KW - Cell proliferation
KW - Extracellular matrix
KW - Glomerular injury
KW - Matrix ligands
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U2 - 10.1046/j.1523-1755.1999.00662.x
DO - 10.1046/j.1523-1755.1999.00662.x
M3 - Article
C2 - 10504498
AN - SCOPUS:0032587573
SN - 0085-2538
VL - 56
SP - 1468
EP - 1480
JO - Kidney international
JF - Kidney international
IS - 4
ER -