GLOMERULAR EXTRACELLULAR-MATRIX COMPONENTS AND INTEGRINS

It has become apparent that extracellular matrix components and their cellular receptors, the integrins, are important regulators of glomeru lar development and function. In this rapidly evolving field we studie d the production of extracellular matrix components and integrins by r at glomerular visceral epithelial and mesangial cells, using molecular probes and antibodies that have recently become available. Special at tention was paid to laminin isoforms and to splice variants of the int egrin subunits alpha 3 and alpha 6. Results were compared to the in vi vo expression in human fetal, newborn and adult kidneys. The mesangial cells were found to produce laminin-1, nidogen and two as yet unident ified laminin isoforms with putative a chains of about 395 (alpha x) a nd of 375 kDa (alpha y), tentatively described before as bovine kidney laminin. Furthermore, they expressed the integrins alpha 1 beta 1, al pha 2 beta 1, alpha 3A beta 1, alpha 5 beta 1, alpha v beta 3, alpha v beta 5, and small amounts of alpha 6A beta 1 and alpha 6B beta 1. The glomerular visceral epithelial cells produced the two new laminin iso forms mentioned above, laminin-5, but no laminin-1 or nidogen. The int egrins alpha 2 beta 1, alpha 3A beta 1, alpha 6A beta 4, alpha 6B beta 4 and the integrin subunit ay were found to be expressed: We show tha t during nephrogenesis, the laminin alpha 1 chain disappears and is re placed by another alpha chain, possibly one of the two as yet unidenti fied alpha chains mentioned above. The laminin beta 1 chain is replace d by the beta 2 chain somewhat later in glomerular development. In gen eral, the integrins found to be expressed in glomeruli of adult kidney were consistent with those found in cultured glomerular visceral epit helial and mesangial cells. No splice variant switch of the integrin a lpha 3 or a6 subunits could be demonstrated during nephrogenesis. Our results suggest an important role for the mesangial cell in providing nidogen as a crucial component of the supramolecular stucture of the g lomerular basement membrane. Furthermore our results indicate that lam inin alpha x beta 2 gamma 1 and alpha y beta 2 gamma 1 isoforms are im portant in the glomerulus of adult kidney and that the integrin alpha 3A beta 1 is the main integrin receptor for laminin isoforms on glomer ular visceral epithelial and mesangial cells, both in vitro and in viv o.