Endothelial Cells and Kidney Regeneration

Dr Jinhua Li

Patients who progress to end-stage renal disease (ESRD) require intensive medical support by dialysis or kidney transplantation.  The past decade has seen a marked increase in the number of patients with newly-diagnosed ESRD, with the majority of new cases being due to diabetic nephropathy and kidney disease related to renovascular disease and hypertension.  Diabetic and non-diabetic glomerular diseases remain the major cause of chronic and ESRD. 

The severity of glomerulosclerosis and tubulointerstitial fibrosis are strong predictors of the progression to ESRD, making this an important target.  Mesangial cells and podocytes are thought to be major mediators of glomerulosclerosis.  The importance of glomerular endothelial cells (GEnCs) in glomerular injury has been largely ignored.  We are interested in understanding how endothelial cells play their critical roles in the pathogenesis of renal injury and fibrosis and how they might initiate kidney regeneration. 

We use several experimental animal models to understand how GEnCs and peritubular capillary endothelial cells (PEnCs) play their critical roles in the pathogenesis of glomerular and tubulointerstitial injury and fibrosis.  We have generated an endothelial-traceble mouse line, Tie2-Cre;loxp-EGFP mice.  Tie2 is an endothelial cell marker.  In this mouse line, the expression of EGFP (Enhanced green fluorescent protein) persists in cells of endothelial origin, despite any subsequent phenotypic changes.  Current experiments utilise streptozotocin-induced diabetic nephropathy and adriamycin-induced nephrosis and unilateral ureteral obstruction models to investigate the roles of endothelial cells in the pathogenesis and regeneration in different disease settings.  We also study the contribution of bone marrow-derived endothelial cells to kidney regeneration together with intracellular mechanism(s) implicated in this process.  In another project, we are investigating how a novel and potent lipid mediator plays its critical role in kidney repair, particularly in endothelial cell regeneration.  Our studies utilize different molecular biology techniques, confocal microscopy and FACS sorting and analysis to explore the roles of renal endothelial cells in kidney injury and repair in depth.

Research Group

Research Assistants

Ms Xinli Qu

Mr Man Lee

Grants & Awards

NHMRC Project Grant:

·       Resolvin E1 is a novel anti-inflammatory and anti-fibrotic lipid mediator for the treatment of chronic kidney disease (2010-2012).

·       New insights into the role of renal endothelial dysfunction in the pathogenesis of glomerular injury and renal fibrosis (2010-2012).

NHMRC Career Development Award: (2010-2013)

Publications

2010

Blockade of endothelial-mesenchymal transition by a Smad3 inhibitor delays the early development of streptozotocin-induced diabetic nephropathy. Diabetes 2010;59(10):2612-24.
Li J, Qu X, Yao J, Caruana G, Ricardo SD, Yamamoto Y, Yamamoto H, Bertram JF.

Resveratrol inhibits renal fibrosis in the obstructed kidney: potential role in deacetylation of Smad3. Am J Pathol 2010;177(3):1065-71.
Li J, Qu X, Ricardo SD, Bertram JF, Nikolic-Paterson DJ.

Review: Endothelial-myofibroblast transition, a new player in diabetic renal fibrosis. Nephrology 2010;15(5):507-12.
Li J, Bertram JF.

SCUBE1, a novel developmental gene involved in renal regeneration and repair. Nephrol Dial Transplant 2010;25(5):1421-8.
Zhuang J, Deane JA, Yang RB, Li J, Ricardo SD.

2009

Endothelial-myofibroblast transition contributes to the early development of diabetic renal interstitial fibrosis in streptozotocin-induced diabetic mice. Am J Pathol 2009;175(4):1380-8.
Li J, Qu X, Bertram JF.

2007

The contribution of bone marrow-derived cells to the development of renal interstitial fibrosis. Stem Cells 2007;25(3):697-706.
Li J, Deane JA, Campanale NV, Bertram JF, Ricardo SD.