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A Selenium-Enriched Ziyang Green Tea Polysaccharide Induces Bax-Dependent Mitochondrial Apoptosis and Inhibits TGF-β1-Stimulated Collagen Expression in Human Keloid Fibroblasts via NG2 Inactivation

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Abstract

Keloids are fibroproliferative disorders characterized by the overabundant deposition of extracellular matrix (ECM), especially collagen and overgrowth of scar tissue in response to cutaneous injury. In this study, we isolated a selenium (Se)-containing polysaccharide (Se-ZGTP-I) from Ziyang green tea and explored its potential therapeutic effects on keloid fibroblasts formation. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and annexin V/propidium iodide (PI) staining assays demonstrated that Se-ZGTP-I or neuron-glia 2 (NG2) short hairpin RNA (shRNA) significantly inhibited proliferation of human keloid fibroblasts via induction of apoptosis. Besides, the activation of caspase-3 and the subsequent cleavage of poly (ADP-ribose) polymerase (PARP) were observed in keloid fibroblasts following Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA treatment. Moreover, Western blotting analysis showed that treatment of keloid fibroblasts with Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA resulted in an increase of pro-apoptotic protein Bax expression and a decrease in expression levels of anti-apoptotic protein Bcl-2 and NG2. In addition, type I collagen biosynthesis and protein expression in keloid fibroblasts following TGF-β1 stimulation were decreased by Se-ZGTP-I (200 and 400 μg/ml) or NG2 shRNA management. Current findings imply that Se-ZGTP-I has a therapeutic potential to intervene and prevent keloid formation and other fibrotic diseases.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81272121 and 81301639).

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Correspondence to Shirong Li or Chuan Cao.

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All patients were informed with written consent, and the study received the approval of the Ethics Committee at the Third Military Medical University.

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The authors declare that they have no conflict of interest.

Additional information

Lele Lu and Linlin Chai contributed equally to this work.

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Lu, L., Chai, L., Wang, W. et al. A Selenium-Enriched Ziyang Green Tea Polysaccharide Induces Bax-Dependent Mitochondrial Apoptosis and Inhibits TGF-β1-Stimulated Collagen Expression in Human Keloid Fibroblasts via NG2 Inactivation. Biol Trace Elem Res 176, 270–277 (2017). https://doi.org/10.1007/s12011-016-0827-8

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  • DOI: https://doi.org/10.1007/s12011-016-0827-8

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