Signal Transduction/Hormone Action
Prevention and Control
Category(ies) of Research
Descriptor of Research
The goal of my research is to investigate if podocyte-specific overexpression of Ang-1 can
prevent and/or treat diabetic nephropathy. Kidney is the main target organ involved in the complications
caused by diabetes mellitus, and diabetic nephropathy is the most common cause of end-stage renal
disease worldwide. The pathogenesis of diabetic nephropathy, however, has not been fully elucidated.
Induced angiogenesis and increased endothelial permeability have been implicated in the development
of hyperfiltration and albuminuria, the hallmarks of the early stage of diabetic nephropathy. More
recently, inflammatory processes including nuclear factor-κB (NF-κB) activation, chemokines and their
receptors upregulation, and macrophage infiltration have emerged as an important factor in the
progression of albuminuria, glomerulosclerosis and interstitial fibrosis in diabetic nephropathy.
Angiopoietins are a family of growth factors which act on endothelial Tie-2 tyrosine kinase receptor.
Angiopoietin-1 (Ang-1) is expressed by podocytes and is a major physiological ligand for Tie2. Ang-1
plays an important role in endothelial cell (EC) survival and EC-pericyte stabilization, thereby reducing
endothelial permeability. It can also antagonize vascular endothelial growth factor functions such as
increasing vascular permeability and inducing angiogenesis. Furthermore, Ang1 has anti-inflammatory
effect by inhibiting monocytes/macrophages infiltration in kidney. Therefore, we hypothesize that the
upregulation of Ang-1 in glomeruli attenuates albuminuria, hyperfiltration and glomerulosclerosis in