title: PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production.
abstract: BACKGROUND
  Oxidative stress is closely associated with cardiac fibrosis. However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction. This study was aimed to investigate the effect of PEP-1-SOD1 fusion protein on angiotensin II (ANG II)-induced collagen metabolism in rat cardiac myofibroblasts (MCFs).
  
  
  METHODS
  MCFs were pretreated with SOD1 or PEP-1-SOD1 fusion protein for 2 h followed by incubation with ANG II for 24 h. Cell proliferation was measured by Cell Counting Kit-8. Superoxide anion productions were detected by both fluorescent microscopy and Flow Cytometry. MMP-1 and TIMP-1 were determined by ELISA. Intracellular MDA content and SOD activity were examined by commercial assay kits. Protein expression was analyzed by western blotting.
  
  
  RESULTS
  PEP-1-SOD1 fusion protein efficiently transduced into MCF, scavenged intracellular O2 (-), decreased intracellular MDA content, increased SOD activity, suppressed ANG II-induced proliferation, reduced expression of TGF-β1, α-SMA, collagen type I and III, restored MMP-1 secretion, and attenuated TIMP-1 secretion.
  
  
  CONCLUSIONS
  PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III. Therefore, PEP-1-SOD1 fusion protein may be a potential novel therapeutic agent for cardiac fibrosis.
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 28621855@qq.com.|Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 28621855@qq.com.
authors.forename: Li-Guo
authors.initials: LG
authors.lastname: Tan
authors.affiliation: Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. xiaojunhui2009@hotmail.com.
authors.forename: Jun-Hui
authors.initials: JH
authors.lastname: Xiao
authors.affiliation: Department of Emergency, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 150694269@qq.com.
authors.forename: Dan-Li
authors.initials: DL
authors.lastname: Yu
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. zlzl_111_1982@163.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 147501729@qq.com.
authors.forename: Fei
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. flinggly@sina.com.
authors.forename: Ling-Yun
authors.initials: LY
authors.lastname: Guo
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. syanghb@163.com.
authors.forename: Jian-Ye
authors.initials: JY
authors.lastname: Yang
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. tangjm416@163.com.|Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. tangjm416@163.com.
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Tang
authors.affiliation: Departments of Physiology and Pharmacology, University of Georgia, Athens, GA, 30622, USA. sc229@uga.edu.
authors.forename: Shi-You
authors.initials: SY
authors.lastname: Chen
authors.affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. rywjn@vip.163.com.|Department of Cardiology, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. rywjn@vip.163.com.
authors.forename: Jia-Ning
authors.initials: JN
authors.lastname: Wang
mesh_terms: D000804:Angiotensin II; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D024042:Collagen Type I / Q000378:metabolism*; D024061:Collagen Type III / Q000378:metabolism*; D003543:Cysteamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D058628:Myofibroblasts / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000494:pharmacology*; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; C503924:Pep-1 peptide; D010455:Peptides; D019715:Tissue Inhibitor of Metalloproteinase-1; D013481:Superoxides; D000804:Angiotensin II; D008315:Malondialdehyde; D003543:Cysteamine; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D020781:Matrix Metalloproteinase 1