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Bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion

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Abstract

Background

Cirrhosis, or liver fibrosis, which is mainly triggered by cirrhosis fat-storing cells (CFSCs) activation, has traditionally been considered an irreversible disease. However, recent observations indicate that even advanced fibrosis is still reversible by removing the causative agents. Anti-fibrotic effects of bone marrow-derived stromal cells (BMSCs) have been demonstrated by inhibiting CFSCs via cytokines secretion; however, the mechanisms are still unclear.

Aims

The purpose of this study was to explore the underlying mechanisms by which BMSCs modulate the function of activated CFSCs.

Methods

After the co-culture of CFSCs with BMSCs supernatants with or without the addition of recombinant rat adrenomedullin (AM)/AM-specific siRNA, western blot analysis was mainly used to detect the differences of relative protein expression on CFSCs.

Results

BMSC-secreted adrenomedullin (AM) effectively inhibited the proliferation and activation of CFSCs by suppressing the expression of Ang II and its binding receptor, AT1, which resulted in a reduction of p47-phox formation.

Conclusions

Our data suggested that BMSCs inhibited CFSC activation in vitro via the AM-Ang II-p47-phox signaling pathway, and since CFSC activation is an essential part of hepatic fibrosis process, this inhibition by BMSCs implies us new insights into the potential treatment of hepatic fibrosis via BMSCs.

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Acknowledgments

The study is financially supported by Heilongjiang Postdoctoral Science-Research Foundation (LBH-Q11034), Provincial department of international research projects (WB07C04), and Key Laboratory of Myocardial Ischemia, Harbin Medical University, Chinese Ministry of Education (KF201202). Natural Science Foundation of Heilongjiang Province of China (C201441).

Conflict of interest

There are no financial interests other than the basic academic employment that the authors have, which could create a conflict of interests or appearance of interests with regard to this work.

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Authors and Affiliations

  1. Emergency Department, The 2nd Affiliated Hospital of Harbin Medical University, 148 Bao Jian Road, Nangang District, Harbin, 150086, China

    Xiaodong Wang

  2. Department of Neurobiology, Harbin Medical University, Heilongjiang Provincial Key Laboratory of Neurobiology, 157 Bao Jian Road, Nangang District, Harbin, 150081, China

    Wei Zhao, Jinghua Wang, Qingfei Kong, Guangyou Wang, Lili Mu, Hulun Li & Bo Sun

  3. Department of Cell Biology, Harbin Medical University, 157 Bao Jian Road, Nangang District, Harbin, 150081, China

    Wei Zhao

  4. Heilongjiang Province Land Reclamation Headquarters General Hostpital, Digestive Department, 235 Hashuang Road, Nangang District, Harbin, 150088, China

    Kexin Shi

  5. The Heilongjiang Province Hospital of Nangang Distinct, The 2nd Ward of Digestion Department, 405 Gogol Street, Harbin, 150001, China

    Xufu Qin

  6. Key Laboratory of Myocardial Ischemia, Harbin Medical University, Chinese Ministry of Education, Harbin, China

    Hulun Li & Bo Sun

  7. Department of Gastroenterology, The 1st Affiliated Hospital of Harbin Medical University, 23 You-Zheng Street, Nangang District, Harbin, 150001, China

    Lijun Shi

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  1. Xiaodong Wang
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  2. Wei Zhao
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  3. Jinghua Wang
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  7. Guangyou Wang
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  8. Lili Mu
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  10. Bo Sun
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  11. Lijun Shi
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Corresponding authors

Correspondence to Bo Sun or Lijun Shi.

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Wang, X., Zhao, W., Wang, J. et al. Bone Marrow Stromal Cells Inhibit the Activation of Liver Cirrhotic Fat-Storing Cells via Adrenomedullin Secretion. Dig Dis Sci 60, 1325–1334 (2015). https://doi.org/10.1007/s10620-014-3423-9

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  • DOI: https://doi.org/10.1007/s10620-014-3423-9

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