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Effect of FIGF overexpression on liver cells transforming to insulin-producing cells

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Abstract

Limitation in the number of insulin-producing pancreatic β-cells is a typical feature of diabetes. It has been indicated that activating pancreatic transcription factors can promote the transformation of hepatocytes into insulin-secreting β-like cells, indicating that direct hepatocyte differentiation seems promising as a treatment for diabetes. Nevertheless, the reprogramming efficiency still remains low. Our previous study found that the expression of c-fos-induced growth factor (FIGF) was increased in the pancreatic tissues in partial pancreatectomy mice compared to that in normal mice. Here, we observed that treatment with Ad-FIGF was found to enhance MafA and Ngn3-induced reprogramming of BNL CL.2 cells to β-like cells with the ability of secreting insulin. And FIGF overexpression increased the levels of histone H3/H4 acetylation at MafA and Ngn3 promoter regions in BNL CL.2 cells. Importantly, in vivo study further confirmed that forced expression of FIGF facilitated the insulin expression and decreased the blood glucose levels in STZ mice. These results strengthen the possibility of developing cell-based therapies for diabetes through utilizing β-like cells derived from non-insulin-secreting cells.

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Abbreviations

Ngn3:

Neurogenin-3

FIGF:

C-fos-induced growth factor

VEGF-D:

Vascular endothelial growth factor-D

DMEM:

Dulbecco’s modified Eagle’s medium

FBS:

Fetal bovine serum

PFA:

Paraformaldehyde

BSA:

Bovine serum albumin

RIPA:

Radioimmunoprecipitation assay

STZ:

Streptozotocin

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Acknowledgements

This study was supported by Project of Ningxia Natural Science Foundation (Grant No.: 2018AAC03264), First-Class Discipline Construction Founded Project of Ningxia Medical University and the School of Clinical Medicine (Grant No.: NXYLXK2017A05) and National Natural Science Foundation of China (Grant No.: 81460152).

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Author notes

  1. Equal contributors.

Authors and Affiliations

  1. Surgery Laboratory, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Yaqin He

  2. Department of Colorectal Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Xiaoliang Xie

  3. College of Clinical Medicine, Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Xiaoliang Xie & Shikuo Rong

  4. Department of Urology, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Xiaoyan Li

  5. Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Yukui Li

  6. Department of Hepatobiliary Surgery, General Hospital of Ningxia Medical University, Yinchuan, 750004, Ningxia, China

    Zhenhui Lu

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  1. Yaqin He
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  2. Xiaoliang Xie
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  3. Xiaoyan Li
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  4. Shikuo Rong
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  5. Yukui Li
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  6. Zhenhui Lu
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Corresponding authors

Correspondence to Yukui Li or Zhenhui Lu.

Additional information

Corresponding editor: Ullas Kolthur-Seetharam

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He, Y., Xie, X., Li, X. et al. Effect of FIGF overexpression on liver cells transforming to insulin-producing cells. J Biosci 44, 149 (2019). https://doi.org/10.1007/s12038-019-9965-4

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