Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway

Zhang,Li‑Ting; Fang,Xue‑Qin; Chen,Qing‑Feng; Chen,Hong; Xiao,Ping; Peng,Xue‑Bin; Zhang,Sheng‑Xiang; Li,Jun‑Feng; Mao,Xiao‑Rong

doi:10.3892/mmr.2015.4362

November-2015 Volume 12 Issue 5

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November-2015 Volume 12 Issue 5

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Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway

Authors:
- Li‑Ting Zhang
- Xue‑Qin Fang
- Qing‑Feng Chen
- Hong Chen
- Ping Xiao
- Xue‑Bin Peng
- Sheng‑Xiang Zhang
- Jun‑Feng Li
- Xiao‑Rong Mao
View Affiliations / Copyright

Affiliations: Department of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Department of Infectious Diseases, The Central Hospital of Baoji, Baoji, Shanxi 721008, P.R. China, Department of Laboratory Medicine, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, Institute of Infectious Diseases, The First Hospital of Lanzhou University, Lanzhou, Gansu 730000, P.R. China, School of Life Science, Lanzhou University, Lanzhou, Gansu 730000, P.R. China

Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
Pages: 7227-7232
|
Published online on: September 25, 2015

https://doi.org/10.3892/mmr.2015.4362
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Abstract

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered to be a potential therapy for end-stage liver disease. However, the therapeutic mechanism of BM-MSCs remains unclear. The aim of the current study was to investigate the role of paracrine signaling in BM‑MSCs in liver cirrhosis in vitro. Human BM‑MSCs and hepatic stellate cells (HSCs) were cultured using a vertical double cell co‑culture system. Groups were divided into HSCs alone (control group) and the co‑culture system of BM‑MSCs with HSCs (experimental group). HSC morphology was observed by inverted phase contrast microscopy. The proliferative capacity of HSCs was measured with the MTT assay and flow cytometry. Hoechst staining was performed to examine the apoptosis of HSCs. Transforming growth factor (TGF)‑β1 and Smad7 mRNA expression were detected by reverse transcription‑quantitative polymerase chain reaction and western blotting. BM‑MSCs did not inhibit the proliferation of HSCs at 24 h, however significantly inhibited the proliferation of HSCs at 48 and 72 h. BM‑MSCs additionally induced the apoptosis of HSCs at 48 h. The concentration of TGF‑β1 in the supernatant at 24 h and 48 h in the co‑cultured system was observed to be significantly lower than in the control group (P<0.05). The level of TGF‑β1 mRNA in the experimental group at 48 h was significantly lower than the control group, however Smad7 mRNA levels were significantly greater than in the control group. Additionally, TGF‑β1 protein levels were significantly lower than in the control group, however levels of Smad7 were greater than the control group. It was concluded that BM‑MSCs are able to inhibit the proliferation and promote the apoptosis of HSCs. In addition, the mechanism may be associated with inhibition of the TGF-β1/Smad pathway in HSCs.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Bone marrow-derived mesenchymal stem cells inhibit the proliferation of hepatic stellate cells by inhibiting the transforming growth factor β pathway

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