title: Recombinant Human Keratinocyte Growth Factor Induces Akt Mediated Cell Survival Progression in Emphysematous Mice.
abstract: BACKGROUND
  Emphysema has been associated with decreased VEGF and VEGFR-2 expression and the presence of high numbers of apoptotic alveolar cells. Keratinocyte growth factor stimulates VEGF synthesis which in turn confers normal lung structure maintenance via the Akt pathway. In this study the potential role of rHuKGF in the improvement of deregulated Akt mediated cell survival pathway in emphysematous mice was investigated.
  
  
  METHODS
  Three experimental groups, i.e., emphysema, treatment and control groups, were prepared. Lungs of mice were treated on 3 occasions by oropharyngeal instillation of 10mg rHuKGF per kg body weight after induction of emphysema with porcine pancreatic elastase. Subsequently, lung tissues from mice were collected for histopathology and molecular biology studies.
  
  
  CONCLUSIONS
  Histopathology photomicrographs and destructive index analysis have shown that elastase-induced airspace enlargement and loss of alveoli recovered in the treatment group. rHuKGF stimulates VEGF production which in turn induces the Akt mediated cell survival pathway in emphysematous lungs. mRNA expression of VEGF, VEGFR, PI3K and Akt was significantly increased while Pten, Caspase-9 and Bad was notably decreased in treatment group when compared with emphysema group, being comparable with the control group. Moreover, VEGF protein expression was in accordance with that found for mRNA.
  
  
  CONCLUSIONS
  Therapeutic rHuKGF supplementation improves the deregulated Akt pathway in emphysema, resulting in alveolar cell survival through activation of the endogenous VEGF-dependent cell survival pathway. Hence rHuKGF may prove to be a potential drug in the treatment of emphysema.
authors.affiliation: Department of Biotechnology, School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India. Electronic address: jmuyal@gbu.ac.in.
authors.forename: Jai
authors.initials: J
authors.lastname: Prakash Muyal
authors.affiliation: Department of Biotechnology, School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
authors.forename: Dhananjay
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Department of Biotechnology, School of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kotnala
authors.affiliation: Department of Internal Medicine, Division of Respiratory Medicine, Philipps-Universität Marburg, Marburg, Alemania; 14/Type V, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
authors.forename: Vandana
authors.initials: V
authors.lastname: Muyal
authors.affiliation: Division of Nuclear Medicine, Institute of Nuclear Medicine and Allied Sciences, Defense Research Development Organization, Nueva Delhi, India.
authors.forename: Amit
authors.initials: A
authors.lastname: Kumar Tyagi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053453:Caspase 9 / Q000096:biosynthesis / Q000235:genetics; D002470:Cell Survival; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007322:Instillation, Drug; D008168:Lung / Q000187:drug effects / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics; D010196:Pancreatic Elastase / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D011656:Pulmonary Emphysema / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011897:Random Allocation; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000096:biosynthesis / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000096:biosynthesis / Q000235:genetics
chemical_list: C494820:Bad protein, mouse; C496453:FGF7 protein, human; D012333:RNA, Messenger; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; D051025:bcl-Associated Death Protein; C467480:vascular endothelial growth factor A, mouse; D051523:Fibroblast Growth Factor 7; D019869:Phosphatidylinositol 3-Kinases; C000592875:Kdr protein, mouse; D040301:Vascular Endothelial Growth Factor Receptor-2; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse; D010196:Pancreatic Elastase; C506434:Casp9 protein, mouse; D053453:Caspase 9
keywords: Akt pathway; Análisis de PCR cuantitativa; Emphysema; Enfisema; Factor de crecimiento queratinocítico humano recombinante; Quantitative PCR analysis; Recombinant human keratinocyte growth factor; Vía de Akt