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Cytoglobin Exhibits Anti-Fibrosis Activity on Liver In Vivo and In Vitro

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Abstract

Cytoglobin, generated using genetic engineering method, is a kind of recombinant human stellate cell activation-associated protein. We speculate that it could influence the development of hepatic fibrosis like Sellate cell activation-associated protein which was discovered by Kawada et al. Therefore, we investigated its anti-fibrosis effect on liver both in vivo and in vitro. During our research, we found that cytoglobin showed obvious effect compared with the control group on Thioacetamide-induced liver fibrosis in SD rats, including significantly decrease in aspartate aminotransferase, Hyaluronic acid, laminin and collagen I(Col I) levels in serum and hydroxyproline in livers, which are the important indices reflecting the degree of hepatic fibrosis. Meanwhile, the viability of rat hepatic stellate cell line T6 (HSC-T6) cells was inhibited by cytoglobin and the apoptosis induced by cytoglobin in HSC-T6 cells was detected by Annexin V/PI double staining. Activation of the caspase cascade including caspase-3 for the intrinsic pathways was demonstrated. The results also showed that the expression of Bcl-2 protein decreased whereas that of Bax protein increased, leading to an increase of the Bax/Bcl-2 ratio. Our results demonstrated that cytoglobin exhibited anti-fibrosis activity on livers in vivo and in vitro, involving apoptosis induction.

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Abbreviations

AST:

Aspartate aminotransferase

Caspases:

cysteine aspartate-specific proteases

Col I:

Collagen I

ECM:

Extracellular matrix

HA:

Hyaluronic acid

hCyt:

Human cytoglobin

HE:

Hematoxylin-eosin

HPLC:

High performance liqid chromatography

HSCs:

Hepatic sellate cells

HSC-T6:

rat hepatic stellate cell line T6

HYP:

Hydroxyproline

LN:

Laminin

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5- diphenytetrazoliumbromide

PS:

Phosphatidylserine

SD rat:

Sprague dawley rat

STAP:

Sellate cell activation-associated protein

TAA:

Thioacetamide

TEM:

Transmission Electron Microscope

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Acknowledgments

The authors thank Professor Qinlong Guo and Lei Tao for assistance.

Conflict of Interest

The authors declare that there are no conflicts of interest.

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Authors and Affiliations

  1. State Key Laboratory of Natural Medicines, Department of Biochemistry, School of Life Science and Technology, China Pharmaceutical University, 24 TongJia Xiang, Nanjing, 210009, People’s Republic of China

    Xin He, Ruoyun Lv, Ke Wang, Wutong Wu & Yu Liu

  2. Department of Pharmacy, School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, People’s Republic of China

    Lifang Yin

  3. Department of Oral Pathology, Nanjing Stomatological Hospital, Affilliated Medical School to Nanjing University, Nanjing, 210008, People’s Republic of China

    Xiaofeng Huang

Authors
  1. Xin He
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  2. Ruoyun Lv
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  3. Ke Wang
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  4. Xiaofeng Huang
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  5. Wutong Wu
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  6. Lifang Yin
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  7. Yu Liu
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Corresponding author

Correspondence to Yu Liu.

Additional information

Xin He and Ruoyun Lv contributed equally to this work.

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He, X., Lv, R., Wang, K. et al. Cytoglobin Exhibits Anti-Fibrosis Activity on Liver In Vivo and In Vitro. Protein J 30, 437–446 (2011). https://doi.org/10.1007/s10930-011-9340-2

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  • DOI: https://doi.org/10.1007/s10930-011-9340-2

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