Lack of α8 integrin leads to morphological changes in renal mesangial cells, but not in vascular smooth muscle cells

Abstract

BackgroundExtracellular matrix receptors of the integrin family are known to regulate cell adhesion, shape and functions. The α8 integrin chain is expressed in glomerular mesangial cells and in vascular smooth muscle cells. Mice deficient for α8 integrin have structural alterations in glomeruli but not in renal arteries. For this reason we hypothesized that mesangial cells and vascular smooth muscle cells differ in their respective capacity to compensate for the lack of α8 integrin.ResultsWild type and α8 integrin-deficient mesangial cells varied markedly in cell morphology and expression or localization of cytoskeletal molecules. In α8 integrin-deficient mesangial cells α-smooth muscle actin and CTGF were downregulated. In contrast, there were no comparable differences between α8 integrin-deficient and wild type vascular smooth muscle cells. Expression patterns of integrins were altered in α8 integrin-deficient mesangial cells compared to wild type mesangial cells, displaying a prominent overexpression of α2 and α6 integrins, while expression patterns of the these integrins were not different between wild type and α8 integrin-deficient vascular smooth muscle cells, respectively. Cell proliferation was augmented in α8 integrin-deficient mesangial cells, but not in vascular smooth muscle cells, compared to wild type cells.ConclusionsOur findings suggest that α8 integrin deficiency has differential effects in mesangial cells and vascular smooth muscle cells. While the phenotype of vascular smooth muscle cells lacking α8 integrin is not altered, mesangial cells lacking α8 integrin differ considerably from wild type mesangial cells which might be a consequence of compensatory changes in the expression patterns of other integrins. This could result in glomerular changes in α8 integrin-deficient mice, while the vasculature is not affected in these mice.

Contribution of the α8 Integrin Chain to the Expression of Extracellular Matrix Components

“…Overexpression of the itga8 did not lead to increases in the expression of matrix components (except for fi bronectin in tubular epithelial cells), but more likely to a downregulation of several matrix molecules. Thus, our results do not argue for an unequivocal profi brotic effect of itga8 expression, neither in mesenchymal nor in epithelial cells, although data from previous experiments (Marek et al, 2010) suggested that the expression of the itga8 might promote a phenotypic change to a more activated mesenchymal phenotype, which is responsible for increased matrix production of cells affected.…”

“…Profi brotic agents like TGF β -1 and angiotensin II are able to induce the expression of the itga8 in different cell types, supporting the notion that α 8 β 1 integrin might exert profi brotic effects (Bouzeghrane et al, 2004;Hartner et al, 1999). Mesangial cells defi cient for the itga8 downregulate the expression of α -smooth muscle actin (a marker of myofi broblast activation) and the profi brotic cytokine CTGF (Marek et al, 2010), further arguing for a contribution of α 8 β 1 90 G. VOLKERT ET AL.…”

“…Altogether, loss of the itga8 did not lead to uniform effects in all experiments, but changed the expression of extracellular matrix and its regulators depending on the cell type and on the kind of knock down of the itga8. These fi ndings could at least partly be explained by differences in compensatory mechanisms after itga8 knock down: For example, in α 8 integrin-defi cient mesangial cells, not in α 8 integrin-defi cient vascular smooth-muscle cells or mesangial cells with a transient knock down of the itga8, an increased expression of the α 2 integrin chain is observed, which might account for at least some of the expressional differences detected in these cells (Marek et al, 2010). However, whether the increase in the expression of the α 2 integrin chain in α 8 integrin-defi cient mesangial cells could result in TGF β -1 upregulation, remains unclear, because α 2 integrin-defi cient mice were shown to have increased TGF β -1 expression levels (Girgert et al, 2010).…”

The Matricellular Protein Cyr61 Is a Key Mediator of Platelet-derived Growth Factor-induced Cell Migration

“…They are composed of integrin ␣ (Itg ␣) and integrin ␤ (Itg ␤) subunits, and each Itg ␣␤ combination has its own signaling properties and binding specificity. A number of integrin subunits, such as ␣v, ␣4, ␣5, ␣6, ␤1, ␤3, ␤4, ␤5, ␣6␤1, and ␣␤3, are expressed in SMCs (33)(34)(35). We found that the specific antibodies against ␣v, ␣6, ␤1, ␤3, ␣6␤1, and ␣␤3 significantly blocked PDGF-BBinduced SMC migration, but the antibodies against ␣4, ␣5, ␤4, and ␤5 had no effect on PDGF-BB-induced SMC migration (Fig.…”

Expression of the Alpha8 Integrin Chain Facilitates Phagocytosis by Renal Mesangial Cells

“…Alpha8 integrin ( Itga8 ) is an RGD binding integrin which is expressed on mesangial cells and regulates their biological properties including adhesion, proliferation, migration and apoptosis by interacting with extracellular ligands such as fibronectin, vitronectin or osteopontin [22, 23]. Its role for phagocytosis is not yet known.…”