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

Abstract

Albumin is filtered into the proximal tubule in large quantities in nephrotic states. It has been proposed that this protein may have a toxic effect on tubular epithelial cells and may be responsible for the initiation of interstitial inflammation and scarring. The mitogenic effect of recombinant human albumin in wild-type opossum kidney cells and in similar cells transfected with a dominant negative p85 subunit (deltap85) of phopshatidylinositide 3-kinase (PI 3-kinase) has been studied. This study demonstrates that recombinant human albumin stimulates proliferation of opossum kidney cells in culture. This effect is mediated via PI 3-kinase, and is inhibited by wortmannin and deltap85 expression. Albumin stimulates PI 3-kinase activity in opossum kidney cells as determined by three different experimental procedures. Recombinant albumin also stimulates pp70(s6) kinase activity in a kinase cascade downstream of PI 3-kinase. Activity of pp70(s6) kinase is essential for albumin-induced proliferation of opossum kidney cells. It is proposed that this mitogenic pathway may have a critical role in proximal tubular homeostasis and pathophysiology of proteinuric states.