Activation of mitogenic pathways by albumin in kidney proximal tubule epithelial cells: Implications for the pathophysiology of proteinuric states

Albumin is filtered into the proximal tubule in large quantities in nephrot ic states. It has been proposed that this protein may have a toxic effect o n tubular epithelial cells and may be responsible for the initiation of int erstitial inflammation and scarring. The mitogenic effect of recombinant hu man albumin in wild-type opossum kidney cells and in similar cells transfec ted with a dominant negative p85 subunit (Delta p85) of phopshatidylinositi de 3-kinase (PI 3-kinase) has been studied. This study demonstrates that re combinant human albumin stimulates proliferation of opossum kidney cells in culture, This effect is mediated via PI 3-kinase, and is inhibited by wort mannin and Delta p85 expression. Albumin stimulates PI 3-kinase activity in opossum kidney cells as determined by three different experimental procedu res. Recombinant albumin also stimulates pp70(s6) kinase activity in a kina se cascade downstream of PT 3-kinase. Activity of pp70(s6) kinase is essent ial for albumin-induced proliferation of opossum kidney cells. It is propos ed that this mitogenic pathway may have a critical role in proximal tubular homeostasis and pathophysiology of proteinuric states.