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2015 ; 15
(ä): 116
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PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin
II-induced collagen production
#MMPMID26446519
Tan LG
; Xiao JH
; Yu DL
; Zhang L
; Zheng F
; Guo LY
; Yang JY
; Tang JM
; Chen SY
; Wang JN
BMC Cardiovasc Disord
2015[Oct]; 15
(ä): 116
PMID26446519
show ga
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-?1, ?-SMA, collagen type I and III,
restored MMP-1 secretion, and attenuated TIMP-1 secretion. CONCLUSION: 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.