PODOCYTES LOOSE THEIR ADHESIVE PHENOTYPE IN FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Podocytes in focal segmental glomerulosclerosis (FSGS) show injury and focal detachment from the glomerular basement membrane (GBM). We stud ied by immunofluorescence and light microscopy the distribution of com ponents involved in the integrin mediated adhesion of podocytes to the GBM in one case of recurrent idiopathic FSGS which developed in a ren al transplant. Two major integrin and actin distribution patterns were observed in podocytes depending on the stage of the disease. Alpha(5) integrin subunit showed a gradual loss in early FSGS and became undet ectable in advanced FSGS. Alpha(3) integrin subunit and the beta(3) su bunit of the vitronectin receptor lost their polarized expression and could be detected intracellularly in early FSGS, while in advanced sta ge both integrin subunits were mostly basally polarized. In addition s taining for alpha(3) was markedly decreased but enhanced for beta(3). Most of the podocytes in early FSGS showed significant loss of filamen tous actin together with a nonpolarized distribution and a transient e xpression of the HAR/GP90 receptor. An altered matrix composition was also seen corresponding to the newly formed GBM. Based on these result s we propose that podocytes loose their adhesive phenotype in early FS GS, which may contribute to the detachment of podocytes from the GBM.