Ying (Maggie) Chen, MD, PhD

Research Interest

Complications

Signal Transduction/Hormone Action

Prevention and Control

Category(ies) of Research

Basic

Translational

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 diabetic nephropathy.