Effect of FIGF overexpression on liver cells transforming to insulin-producing cells
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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.
KeywordsC-fos-induced growth factor (FIGF) diabetes histone H3/H4 acetylation MafA and Ngn3
C-fos-induced growth factor
Vascular endothelial growth factor-D
Dulbecco’s modified Eagle’s medium
Fetal bovine serum
Bovine serum albumin
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).
- Davydova N, Harris N, Roufail S, Paquet-Fifield S, Ishaq M, Streltsov V, Williams S, Karnezis T, et al. 2016 Differential receptor binding and regulatory mechanisms for the lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and -D. J. Biol. Chem. 291 27265–27278CrossRefGoogle Scholar
- Jauhiainen S, Häkkinen S, Toivanen P, Heinonen S, Jyrkkänen H, Kansanen E, Leinonen H, Levonen A, et al. 2011 Vascular endothelial growth factor (VEGF)-D stimulates VEGF-A, stanniocalcin-1, and neuropilin-2 and has potent angiogenic effects. Arterioscler. Thromb. Vasc. Biol. 31 1617–1624CrossRefGoogle Scholar
- Rutanen J, Rissanen T, Markkanen J, Gruchala M, Silvennoinen P, Kivelä A, Hedman A, Hedman M, et al. 2004 Adenoviral catheter-mediated intramyocardial gene transfer using the mature form of vascular endothelial growth factor-D induces transmural angiogenesis in porcine heart. Circulation 109 1029–1035CrossRefGoogle Scholar
- Teng ZG, Wei J and Fan H 2012 The important role of c-fos-induced growth factor in the pancreas regeneration. Chin. J. Diabetes 5 373–376Google Scholar