The α8 integrin chain affords mechanical stability to the glomerular capillary tuft in hypertensive glomerular disease

In the kidney, the alpha8 integrin chain is expressed in glomerular mesangial cells. The alpha8 integrin plays a role in early nephrogenesis but its functional role in the adult kidney is unknown. We tested the hypothesis that alpha8 integrin-mediated cell-matrix interactions are important to maintain the integrity of the glomerulus in arterial hypertension. Desoxycorticosterone (DOCA)-salt hypertension was induced in mice homozygous for a deletion of the alpha8 integrin chain and wild-type mice. Blood pressure, albumin excretion, total renal mass, and glomerular filtration in DOCA-treated alpha8-deficient mice were comparable to DOCA-treated wild types. DOCA-treated wild types showed increased glomerular immunostaining for alpha8 integrin compared to salt-loaded and untreated controls, whereas the glomeruli of alpha8-deficicnt mice always stained negative. Morphometric studies revealed similar degrees of glomerulosclerosis in DOCA-treated alpha8-deficient and DOCA-treated wild-type mice. However, DOCA-treated alpha8-deficient mice had a higher score of capillary widening (mesangiolysis) than DOCA-treated wild-type mice, which was confirmed in two additional wild-type strains. Moreover, in DOCA-treated alpha8-deficient mice, glomerular fibrin deposits were more frequent than in DOCA-treated wild types. The results show that lack of alpha8 is associated with increased susceptibility to glomerular capillary destruction in DOCA salt hypertension, whereas it does not seem to play a major role in the development of fibrosis or glomerulosclerosis. Our findings indicate that mesangial alpha8 integrin contributes to maintain the integrity of the glomerular capillary tuft during mechanical stress, eg, in hypertension.