title: Hepatocyte growth factor gene therapy enhances infiltration of macrophages and may induce kidney repair in db/db mice as a model of diabetes.
abstract: OBJECTIVE
  We previously demonstrated hepatocyte growth factor (HGF) gene therapy was able to induce regression of glomerulosclerosis in diabetic nephropathy through local reparative mechanisms. The aim of this study was to test whether bone-marrow-derived cells are also involved in this HGF-induced reparative process.
  
  
  METHODS
  We have created chimeric db/db mice as a model of diabetes that produce enhanced green fluorescent protein (EGFP) in bone marrow cells. We performed treatment with HGF gene therapy either alone or in combination with granulocyte-colony stimulating factor, in order to induce mobilisation of haematopoietic stem cells in these diabetic and chimeric animals.
  
  
  RESULTS
  We find HGF gene therapy enhances renal expression of stromal-cell-derived factor-1 and is subsequently associated with an increased number of bone-marrow-derived cells getting into the injured kidneys. These cells are mainly monocyte-derived macrophages, which may contribute to the renal tissue repair and regeneration consistently observed in our model. Finally, HGF gene therapy is associated with the presence of a small number of Bowman's capsule parietal epithelial cells producing EGFP, suggesting they are fused with bone-marrow-derived cells and are contributing to podocyte repopulation.
  
  
  CONCLUSIONS
  Altogether, our findings provide new evidence about the therapeutic role of HGF and open new opportunities for inducing renal regeneration in diabetic nephropathy.
authors.affiliation: Nephrology Laboratory, Departament de Ciències Clíniques, IDIBELL, University of Barcelona, Bellvitge Hospital, Barcelona, Spain.
authors.forename: M
authors.initials: M
authors.lastname: Flaquer
authors.forename: M
authors.initials: M
authors.lastname: Franquesa
authors.forename: A
authors.initials: A
authors.lastname: Vidal
authors.forename: N
authors.initials: N
authors.lastname: Bolaños
authors.forename: J
authors.initials: J
authors.lastname: Torras
authors.forename: N
authors.initials: N
authors.lastname: Lloberas
authors.forename: I
authors.initials: I
authors.lastname: Herrero-Fresneda
authors.forename: J M
authors.initials: JM
authors.lastname: Grinyó
authors.forename: J M
authors.initials: JM
authors.lastname: Cruzado
mesh_terms: D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000627:therapeutic use*; D022781:Hepatocytes / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism / Q000628:therapy*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic
chemical_list: D017228:Hepatocyte Growth Factor