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PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production.

Tan LG, Xiao JH, Yu DL, Zhang L, Zheng F, Guo LY, Yang JY, Tang JM, Chen SY, Wang JN - BMC Cardiovasc Disord (2015)

Bottom Line: However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction.Protein expression was analyzed by western blotting.PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 28621855@qq.com.

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.

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.

No MeSH data available.


Related in: MedlinePlus

Effect of PEP-1-SOD1 on matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase 1 (TIMP-1) secretion. The levels of MMP-1 (a) and TIMP-1 (b) in culture media were examined by ELISA. *P < 0.01 vs. vehicle-treated cells, #P < 0.01 vs. Ang II-treated cells, &P < 0.01 vs. SOD1- transduced cells n = 5
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Fig6: Effect of PEP-1-SOD1 on matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase 1 (TIMP-1) secretion. The levels of MMP-1 (a) and TIMP-1 (b) in culture media were examined by ELISA. *P < 0.01 vs. vehicle-treated cells, #P < 0.01 vs. Ang II-treated cells, &P < 0.01 vs. SOD1- transduced cells n = 5

Mentions: MMP-1 is a crucial enzyme degrading ECM, and TIMP-1 is a key inhibitor of MMPs. The production of MMP-1 and TIMP-1 is associated with cardiac fibrosis. We found that Ang II reduced the MMP-1 secretion and stimulated production of TIMP-1 in MCF (Fig. 6a-b), consistent with the increased production of Col I and Col III. Pretreatment of SOD1 only marginally reversed Ang II-mediated increase of MMP-1 and reduction of TIMP-1 (Fig. 6a-b). Pretreatment of PEP-1-SOD1, however, almost completely restored Ang II-blocked MMP-1 secretion, and dramatically inhibited Ang II-mediated increase of TIMP-1 secretion (Fig. 6a-b).Fig. 6


PEP-1-SOD1 fusion proteins block cardiac myofibroblast activation and angiotensin II-induced collagen production.

Tan LG, Xiao JH, Yu DL, Zhang L, Zheng F, Guo LY, Yang JY, Tang JM, Chen SY, Wang JN - BMC Cardiovasc Disord (2015)

Effect of PEP-1-SOD1 on matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase 1 (TIMP-1) secretion. The levels of MMP-1 (a) and TIMP-1 (b) in culture media were examined by ELISA. *P < 0.01 vs. vehicle-treated cells, #P < 0.01 vs. Ang II-treated cells, &P < 0.01 vs. SOD1- transduced cells n = 5
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4597385&req=5

Fig6: Effect of PEP-1-SOD1 on matrix metalloproteinase-1 (MMP-1) and tissue inhibitors of metalloproteinase 1 (TIMP-1) secretion. The levels of MMP-1 (a) and TIMP-1 (b) in culture media were examined by ELISA. *P < 0.01 vs. vehicle-treated cells, #P < 0.01 vs. Ang II-treated cells, &P < 0.01 vs. SOD1- transduced cells n = 5
Mentions: MMP-1 is a crucial enzyme degrading ECM, and TIMP-1 is a key inhibitor of MMPs. The production of MMP-1 and TIMP-1 is associated with cardiac fibrosis. We found that Ang II reduced the MMP-1 secretion and stimulated production of TIMP-1 in MCF (Fig. 6a-b), consistent with the increased production of Col I and Col III. Pretreatment of SOD1 only marginally reversed Ang II-mediated increase of MMP-1 and reduction of TIMP-1 (Fig. 6a-b). Pretreatment of PEP-1-SOD1, however, almost completely restored Ang II-blocked MMP-1 secretion, and dramatically inhibited Ang II-mediated increase of TIMP-1 secretion (Fig. 6a-b).Fig. 6

Bottom Line: However, the effect of copper, zinc-superoxide dismutase (SOD1) as a therapeutic agent is limited due to the insufficient transduction.Protein expression was analyzed by western blotting.PEP-1-SOD1 suppressed MCF proliferation and differentiation and reduced production of collagen type I and III.

View Article: PubMed Central - PubMed

Affiliation: Institute of Clinical Medicine, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, P. R. China. 28621855@qq.com.

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.

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.

No MeSH data available.


Related in: MedlinePlus