title: Phosphocreatine attenuates angiotensin II-induced cardiac fibrosis in rat cardiomyocytes through modulation of MAPK and NF-κB pathway.
abstract: Transforming growth factor β (TGF-β) plays crucial roles in Ang II-induced cardiac fibrosis (CF). Phosphocreatine (PCr), one of the important players involved in cellular energy metabolism, is widely used in the treatment of clinical heart failure. However, whether it participates in CF is still unclear. This study aimed to identify the mechanisms involved in PCr and CF.
  
  
  
  Rat cardiomyocytes (H9C2) were induced by Ang II followed by treatment of PCr. ERK1 siRNA, ERK2 siRNA and NF-κB siRNA were applied to identify the molecular mechanism. Then CF-related proteins were analyzed by western blot and real-time PCR to confirm the influence of the mechanisms involved in PCr.
  
  
  
  PCr did protect cardiomyocytes from Ang II-induced fibrosis. Meanwhile, PCr suppressed Ang II-induced up-regulation of TGF-β. By detecting TGFβ-mediated or MAPK pathway associated proteins, PCr inhibited MAPK and NF-κB pathway, thus suppressed Ang II-induced cardiac fibrosis, which was further confirmed by siRNA transfection.
  
  
  
  Our study determined that PCr protected cardiomyocytes from Ang II-induced CF through inhibition of MAPK and NF-κB pathway.
authors.affiliation: Department of Emergency, Xinhua Hospital of Shanghai Jiaotong University, Shanghai, China. panshuming1357@sina.com.
authors.forename: A-H
authors.initials: AH
authors.lastname: Fei
authors.forename: F-C
authors.initials: FC
authors.lastname: Wang
authors.forename: Z-B
authors.initials: ZB
authors.lastname: Wu
authors.forename: S-M
authors.initials: SM
authors.lastname: Pan
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D020935:MAP Kinase Signaling System; D032383:Myocytes, Cardiac / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism / Q000494:pharmacology*; D034741:RNA, Small Interfering; D051381:Rats; D051996:Transcription Factor RelA / Q000378:metabolism
chemical_list: D016328:NF-kappa B; C498143:RELA protein, human; D034741:RNA, Small Interfering; D051996:Transcription Factor RelA; D010725:Phosphocreatine; D000804:Angiotensin II