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The Role of Phospholipase D1 in Liver Fibrosis Induced by Dimethylnitrosamine In Vivo

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Abstract

Background

Phospholipase D (PLD) has been proved to be involved in regulating function of fibroblasts and might play a role in mediating organic fibrosis.

Aims

To investigate the role and mechanism of PLD on dimethylnitrosamine (DMN)-induced rat liver fibrosis.

Methods

Fifty-five male Wistar rats were divided into normal control group, DMN model group, N-methylethanolamine (MEA) control group, and MEA-intervention group. We observed the effects of MEA, a PLD inhibitor on the development and progression of rat liver fibrosis by comparing the physical and biochemical indexes, tissue pathology, PLD activity, and typical markers and cytokines related to fibrosis in the four groups.

Results

Accompanied by the down-regulation of PLD1 expression, the MEA-intervention group had improved outcomes compared with the DMN model group in terms of spleen weight, spleen/weight index, serum and tissue biochemical indexes, tissue hydroxyproline, and tissue pathology. The MEA-intervention group had lower TIMP1, COL1A1, and higher MMPs expression level than the DMN model group. The activity of PLD and PLD1, α-SMA expression level in the MEA-intervention group was much lower than those in the DMN model group. There was no significant difference between the two groups in the expression level of TGF-β1 and MCP1. Meanwhile, there were no significant differences between normal control group and MEA control group in the parameters stated above.

Conclusion

Phospholipase D1 may play an important role in the development and progression of rat liver fibrosis. Inhibition of PLD may become a new strategy to prevent or alleviate liver fibrosis.

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Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 81170406), Shanghai Natural Science Foundation by Shanghai Science and Technology Commission (No. 11ZR1433500), and the Wangbaoen Fund of Chinese Foundation for Hepatitis Prevention and Control (No. 20100029).

Conflict of interest

None.

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Authors and Affiliations

  1. Department of Gastroenterology and Digestive diseases Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China

    Xinyan Zhu, Dapeng Kuang, Jingqi Liu, Xiaomeng Shi, Tingting Zhang & Wenzhuo Yang

  2. Department of Respiratory Diseases, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China

    Ruilin Liu

  3. Department of Pathology, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China

    Yu Zeng

  4. Department of Central Laboratory, Shanghai Tongji Hospital, Tongji University School of Medicine, Shanghai, 200065, China

    Xianghua Sun & Yi Zhang

  5. Department of Gastroenterology and Digestive Diseases Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai, 200062, China

    Wenzhuo Yang

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  1. Xinyan Zhu
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  2. Ruilin Liu
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  3. Dapeng Kuang
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  7. Yu Zeng
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Corresponding author

Correspondence to Wenzhuo Yang.

Additional information

Xinyan Zhu and Ruilin Liu contributed equally to this work.

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Zhu, X., Liu, R., Kuang, D. et al. The Role of Phospholipase D1 in Liver Fibrosis Induced by Dimethylnitrosamine In Vivo. Dig Dis Sci 59, 1779–1788 (2014). https://doi.org/10.1007/s10620-014-3130-6

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  • DOI: https://doi.org/10.1007/s10620-014-3130-6

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