Feng Wei

Publications (2)11.38 Total impact

• Article: Neutrophil gelatinase-associated lipocalin suppresses cyst growth by Pkd1 null cells in vitro and in vivo.

  Feng Wei, Anil Karihaloo, Zhiheng Yu, Arnaud Marlier, Pankaj Seth, Sekiya Shibazaki, Tong Wang, Vikas P Sukhatme, Stefan Somlo, Lloyd G Cantley
  [show abstract] [hide abstract]
  ABSTRACT: Cyst growth in patients with autosomal dominant polycystic kidney disease is thought to be due to increased tubular cell proliferation. One model to explain this altered proliferation suggests that the polycystin proteins PC1 and PC2 localize to apical cilia and serve as an integral part of the flow-sensing pathway thus modulating the proliferative response. We measured proliferation and apoptosis in proximal tubule derived cell lines lacking PC1. These cells showed increased rates of proliferation, a decreased rate of apoptosis, compared to control heterozygous cell lines, and spontaneously formed cysts rather than tubules in an in vitro tubulogenesis assay. Addition of neutrophil gelatinase associated lipocalin (NGAL), a small secreted protein that binds diverse ligands, to the cells lacking PC1 inhibited proliferation and increased apoptosis leading to slower cyst growth in vitro. Sustained over-expression at low level of NGAL by an adenoviral delivery system suppressed cyst enlargement without improving renal function in the Pkd1 mutant mice. Our studies show that renal epithelial cells lacking PC1 have an inherent tendency to hyper-proliferate forming cysts in vitro independent of a flow stimulus. The potential benefit of attenuating cyst growth with NGAL remains to be determined.
  Kidney International 12/2008; 74(10):1310-8. · 6.61 Impact Factor
• Article: Expression of neutrophil gelatinase-associated lipocalin regulates epithelial morphogenesis in vitro.

  Jane A Gwira, Feng Wei, Shuta Ishibe, Joseph M Ueland, Jonathan Barasch, Lloyd G Cantley
  [show abstract] [hide abstract]
  ABSTRACT: Growth factors such as hepatocyte growth factor (HGF) are highly up-regulated during development and following renal injury and are known to induce marked morphogenic actions in cultured tubular epithelial cells, including scattering, migration, single cell branching morphogenesis, and multicellular branching tubulogenesis. In the present study, we demonstrate that HGF stimulates epithelial cells to express neutrophil gelatinase-associated lipocalin (Ngal), a member of the lipocalin family of secreted proteins that has recently been shown to participate in mesenchymal-epithelial transformation via its ability to augment cellular iron uptake. At concentrations below those found to mediate iron transport, purified Ngal can induce a promigratory and probranching effect that is dependent on ERK activation. The suppression of Ngal expression using short hairpin RNA results in increased cyst formation by tubular cells. However, the simultaneous addition of Ngal and HGF leads to direct association of the two proteins, and results in a partial inhibition of HGF-mediated activation of c-Met and the downstream MAPK and phosphatidylinositol 3-kinase signaling pathways. This inhibitory effect down-regulates HGF-stimulated single cell migration, and limits branching morphogenesis at both the single cell and multicellular level. These experiments demonstrate that the local expression of Ngal can play a regulatory role in epithelial morphogenesis by promoting the organization of cells into tubular structures while simultaneously negatively modulating the branching effects of HGF.
  Journal of Biological Chemistry 04/2005; 280(9):7875-82. · 4.77 Impact Factor