title: Effect of recombinant human keratinocyte growth factor in inducing Ras-Raf-Erk pathway-mediated cell proliferation in emphysematous mice lung.
abstract: BACKGROUND
  Pulmonary emphysema is resulted due to destruction of the structure of the alveoli. Recently, exogenous recombinant human Keratinocyte growth factor (rHuKGF) has been reported to induce the regeneration of gas exchange structures. However, the molecular mechanisms governing this process are so far unknown.
  
  
  OBJECTIVE
  The objective of this study was to investigate the effect of rHuKGF in the lungs of emphysema-challenged mice on Ras-Raf-Erk (Erk, extracellular signal-regulated kinase) mediated signaling pathway that regulates alveolar epithelial cell proliferation.
  
  
  METHODS
  Three experimental groups (i.e. emphysema, therapy and control group) were prepared. Lungs of mice were therapeutically treated at three occasions by oropharyngeal instillation of 10 mg rHuKGF per kg body weight after induction of emphysema by porcine pancreatic elastase (PPE). Subsequently, lung tissues from each mouse 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 were recovered in therapy group. Moreover, proliferating cell nuclear antigen (PCNA) at mRNA and protein expression level was markedly increased in therapy group than emphysema group. Upon validation at mRNA level, expressions of FGF-7, FGF-R, Ras, c-Raf, Erk-1, Erk-2, c-Myc and were significantly increased, whereas Elk-1 was notably decreased in therapy group when compared with emphysema group and were well comparable with the control group.
  
  
  CONCLUSIONS
  Therapeutic supplementation of rHuKGF rectifies the deregulated Ras-Raf-Erk pathway in emphysema condition, resulting in alveolar epithelium regeneration. Hence, rHuKGF may prove to be a potential drug in the treatment of emphysema.
authors.affiliation: School of Biotechnology, Gautam Buddha University , Greater Noida, Uttar Pradesh , India and.
authors.forename: Jai Prakash
authors.initials: JP
authors.lastname: Muyal
authors.forename: Sudhir
authors.initials: S
authors.lastname: Kotnala
authors.forename: Harsh
authors.initials: H
authors.lastname: Bhardwaj
authors.forename: Amit
authors.initials: A
authors.lastname: Tyagi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D006801:Humans; D008168:Lung / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000502:physiology; D011656:Pulmonary Emphysema / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology
chemical_list: C496453:FGF7 protein, human; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7; C496354:Fgfr2 protein, mouse; D051497:Receptor, Fibroblast Growth Factor, Type 2
keywords: Alveolar regeneration; Ras–Raf–Erk pathway; emphysema; rHuKGF