Role of α8 integrin in mesangial cell adhesion, migration, and proliferation

Abstract

Background. Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, migration, and proliferation. The α8 integrin chain is expressed in the glomerulus exclusively by mesangial cells. The contribution of α8 to mesangial cell function, however, has not yet been studied. Methods. Mesangial cells from wild-type and α8-deficient mice were isolated and characterized. Integrin expression was assessed by real-time polymerase chain reaction (PCR), Western blot, or fluorescence-activated cell sorter (FACS) analysis. Cell adhesion was determined by conventional attachment assay and a centrifugal assay for cell adhesion. Cell migration was determined by a fluorescence-based transmigration assay and a chemotaxis assay. Proliferation rates were determined by BrdU and [3H]-thymidine assays. Results. On the α8 ligands fibronectin and vitronectin, but not on collagens, attachment of α8-deficient mesangial cells was reduced compared to wild-type cells. In contrast, α8-deficient mesangial cells migrated more easily and displayed an increased proliferative response on fibronectin or vitronectin, but not on collagens, compared to wild-type cells. These effects were not due to an up-regulation of the fibronectin or vitronectin receptors α5 or αv in α8-deficient mesangial cells, as the cell surface expression of integrins α5 and αv was comparable in wild-type and α8-deficient mesangial cells. Conclusion. These findings confirm a role for α8 integrin in the regulation of the mesangial cell phenotype, α8 integrin seems to promote adhesion, but inhibit migration and proliferation of mesangial cells. Thus, the data support the hypothesis that α8 integrin could play an important role for maintaining tissue integrity in the glomerulus during glomerular injury.