Role of alpha8 integrin in mesangial cell adhesion, migration, and proliferation.
BACKGROUND
Extracellular matrix receptors of the integrin family are known to regulate cell adhesion, migration, and proliferation. The alpha8 integrin chain is expressed in the glomerulus exclusively by mesangial cells. The contribution of alpha8 to mesangial cell function, however, has not yet been studied.


METHODS
Mesangial cells from wild-type and alpha8-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 alpha8 ligands fibronectin and vitronectin, but not on collagens, attachment of alpha8-deficient mesangial cells was reduced compared to wild-type cells. In contrast, alpha8-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 alpha5 or alphav in alpha8-deficient mesangial cells, as the cell surface expression of integrins alpha5 and alphav was comparable in wild-type and alpha8-deficient mesangial cells.


CONCLUSIONS
These findings confirm a role for alpha8 integrin in the regulation of the mesangial cell phenotype. alpha8 integrin seems to promote adhesion, but inhibit migration and proliferation of mesangial cells. Thus, the data support the hypothesis that alpha8 integrin could play an important role for maintaining tissue integrity in the glomerulus during glomerular injury.
Bieritz
Beate
B
Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany.
Spessotto
Paola
P
Colombatti
Alfonso
A
Jahn
Angelika
A
Prols
Felicitas
F
Hartner
Andrea
A
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003094:Collagen; D005353:Fibronectins; D005920:Glomerular Mesangium / Q000166:cytology / Q000502:physiology*; D006801:Humans; D039001:Integrin alpha Chains / Q000172:deficiency / Q000502:physiology*; D039482:Integrin alpha5 / Q000378:metabolism; D039564:Integrin alphaV / Q000378:metabolism; D008024:Ligands; D051379:Mice; D010641:Phenotype; D013936:Thymidine / Q000378:metabolism; D014746:Vimentin
D005353:Fibronectins; D039001:Integrin alpha Chains; D039482:Integrin alpha5; D039564:Integrin alphaV; D008024:Ligands; D014746:Vimentin; C093856:integrin alpha8; D003094:Collagen; D013936:Thymidine