title: Systemic administration of naked plasmid encoding HGF attenuates puromycin aminonucleoside-induced damage of murine glomerular podocytes.
abstract: Podocyte injury is considered to play important roles in the pathogenesis of human glomerular disease. There is accumulating evidence suggesting that hepatocyte growth factor (HGF) elicits preventive activity for glomerular cells in animal models of chronic renal diseases. In this study, we demonstrated that delivery of a naked plasmid vector encoding the human HGF gene into mice by a hydrodynamic-based in vivo gene transfection approach markedly reduced proteinuria and attenuated podocyte injury in a mouse model induced by puromycin aminonucleoside (PAN) injection. Systemic administration by rapid injection via the tail vein of a naked plasmid containing HGF cDNA driven under a cytomegalovirus promoter (pCMV-HGF) produced a remarkable level of human HGF protein in the circulation. Tissue distribution studies suggested that the kidney expressed a high level of the HGF transgene. Meanwhile, compared with tubules and interstitium, a higher level of exogenous HGF protein was detected in the glomeruli. Administration of pCMV-HGF dramatically abated the urine albumin excretion and podocyte injury in PAN nephropathy in mice. Exogenous expression of HGF produced evidently beneficial effects, leading to restoration of Wilms' tumor-1 (WT1) and α-actinin-4 expression and attenuation of ultrastructural damage of the podocytes. In vitro, HGF not only restored WT1 and α-actinin-4 expression but also inhibited albumin leakage of podocytes incubated with PAN in a Transwell culture chamber. These results suggest that HGF might provide a novel strategy for amelioration of podocyte injury.
authors.affiliation: Center of Kidney Disease, 2nd Affiliated Hospital, Nanjing Medical University, Nanjing, China.
authors.forename: Xuan
authors.initials: X
authors.lastname: Bu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Hua
authors.initials: H
authors.lastname: Zhang
authors.forename: Wenjing
authors.initials: W
authors.lastname: Qiu
authors.forename: Lu
authors.initials: L
authors.lastname: Chen
authors.forename: Hongdi
authors.initials: H
authors.lastname: Cao
authors.forename: Li
authors.initials: L
authors.lastname: Fang
authors.forename: Ping
authors.initials: P
authors.lastname: Wen
authors.forename: Ruoyun
authors.initials: R
authors.lastname: Tan
authors.forename: Junwei
authors.initials: J
authors.lastname: Yang
mesh_terms: D000185:Actinin / Q000096:biosynthesis; D000419:Albuminuria / Q000473:pathology* / Q000628:therapy*; D000818:Animals; D019610:Cytoprotection; D017228:Hepatocyte Growth Factor / Q000235:genetics*; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids / Q000008:administration & dosage* / Q000235:genetics; D050199:Podocytes / Q000187:drug effects / Q000473:pathology*; D011692:Puromycin Aminonucleoside / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D025721:WT1 Proteins / Q000096:biosynthesis
chemical_list: C491752:Actn4 protein, mouse; C066855:HGF protein, human; D025721:WT1 Proteins; D000185:Actinin; D011692:Puromycin Aminonucleoside; D017228:Hepatocyte Growth Factor