GLUCOSE-INDUCED ALTERATION OF INTEGRIN EXPRESSION AND FUNCTION IN CULTURED HUMAN MESANGIAL CELLS

Alteration in mesangial volume, due to an increase of the matrix surro unding mesangial cells, is a hallmark indicator of nephropathy in diab etes. Mesangial cells may also play a significant role in the developm ent of nephropathy. Therefore, we examined the effect of glucose on th e expression of integrins by cultured human mesangial cells and their ability to interact with collagen IV, a major component of the mesangi al matrix. Human mesangial cells were grown in 5 and 25 mM glucose and their integrin profile was examined by immunoprecipitation and flow c ytometry in each experimental condition. The results indicate that whe n mesangial cells were grown in 25 mM glucose, the expression of integ rin subunit alpha 2, was increased, while the alpha 1 subunit was cons iderably decreased, as compared to cells grown in 5 mM glucose. Additi onally, mesangial cells were tested for their ability to adhere to col lagen IV in a solid-phase assay in the presence of neutralizing antibo dies to integrin subunits. The results of these experiments indicate t hat both alpha 1 and alpha 2 complexed to beta 1 (alpha 2 beta 1 and a lpha 1 beta 1) are major mesangial cell receptors for adhesion to coll agen IV both in 5 and 25 mM glucose. The two receptors act in concert to mediate adhesion of mesangial cells to type IV collagen. When cell surface expression of the alpha 1 subunit in 25 mM glucose was reduced , the alpha 2 subunit was involved in adhesion to a greater extent tha n it was in 5 mM glucose. Immunoperoxidase histochemical studies local ized both al and alpha 2 integrin subunits in the mesangium of normal adult kidneys, suggesting that in vivo interaction with collagen IV co uld involve both of these receptors. These observations suggest that g lucose-induced alterations in integrin expression may modify the abili ty of mesangial cells to interact with collagen IV.