Selective binding of integrins from different renal cell types to the NC1 domain of alpha3 and alpha1 chains of type IV collagen.
BACKGROUND
Cells interact with type IV collagen (Col IV) via integrins through the triple-helical and NC1 domains. We examined interactions of human glomerular and proximal tubular epithelial cells with recombinant alpha1 and alpha3 NC1 chains of Col IV, to explore the ability of different cell types to interact with Col IV of different trimer composition.


METHODS
Interactions of TSV-40-immortalized human glomerular epithelial cells (HGECs), HPV-16-immortalized human proximal tubular epithelial (HK-2) cells and primary human mesangial cells (MES) with recombinant alpha1 and alpha3 NC1 chains of Col IV were examined by affinity chromatography and solid-phase binding assays. The expression of integrin-regulated metalloproteinases was examined by zymography.


RESULTS
HGECs bound to both alpha3 and alpha1(IV)NC1, albeit there was preferential binding to alpha3(IV)NC1, through the alpha3beta1 and alpha2beta1 integrin receptors; HK-2 cells and MES bound almost exclusively to alpha1(IV)NC1 via the alpha3beta1/alphavbeta3 and alpha1beta1/alpha2beta1 receptors, respectively. It was demonstrated that the expression of MMP-2 and MMP-9 by HGECs was down-regulated in the presence of alpha3(IV)NC1.


CONCLUSIONS
The observed data indicate that the isoform NC1 chains of Col IV serve for selective, integrin-mediated cell binding which probably triggers different signaling mechanisms, resulting in the activation of specific transcription factors and the modulation of gene expression.
Aggeli
Athanasia S
AS
Institute of Biology, National Centre for Scientific Research Demokritos, Agia Paraskevi, Athens, Greece.
Kitsiou
Paraskevi V
PV
Tzinia
Athina K
AK
Boutaud
Ariel
A
Hudson
Billy G
BG
Tsilibary
Effie C
EC
D001324:Autoantigens / Q000378:metabolism*; D002460:Cell Line; D024141:Collagen Type IV / Q000378:metabolism*; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D006801:Humans; D039222:Integrin alpha1beta1 / Q000378:metabolism; D038982:Integrin alpha2beta1 / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D007678:Kidney Glomerulus / Q000166:cytology / Q000378:metabolism*; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000378:metabolism*; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D050527:Mesangial Cells / Q000166:cytology / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms; D015398:Signal Transduction
D001324:Autoantigens; D024141:Collagen Type IV; D039222:Integrin alpha1beta1; D038982:Integrin alpha2beta1; D016023:Integrins; D020033:Protein Isoforms; C057112:type IV collagen alpha3 chain; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9