Alterations in tubular epithelial cells in diabetic nephropathy.

In this report, we show that kidney sections of diabetic patients express higher levels of phospho-tuberin (inactive form of tuberin), and that is associated with an increase in mTOR activation as measured by phosphorylation level of p70S6K. Inactivation of tuberin and activation of mTOR lead to accumulated cell matrix proteins (fibronectin and collagen IV) mainly in tubular epithelial cells of the kidneys of diabetic patients. In addition, significant staining of vimentin as a marker of cells undergoing an epithelial-to-mesenchymal transition (EMT) was detected in kidney sections of diabetic patients. On the other hand, very weak or nondetectable staining of cell matrix proteins, p-tuberin and P-p70S6K as well as vimentin was found in normal kidney sections of healthy subjects. The morpho...