Surgery Laboratory, General Hospital of Ningxia Medical University, Yinchuan 750004, Ningxia, China.
J Biosci. 2019 Dec;44(6).
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, 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.
胰岛β细胞数量的限制是糖尿病的一个典型特征。有研究表明，激活胰腺转录因子可以促进肝细胞向胰岛素分泌β样细胞的转化，这表明直接诱导肝细胞分化似乎是治疗糖尿病的一种有前途的方法。然而，重编程效率仍然很低。我们之前的研究发现，与正常小鼠相比，部分胰腺切除小鼠的胰腺组织中 c-fos 诱导生长因子 (FIGF) 的表达增加。在这里，我们观察到，Ad-FIGF 的处理被发现可以增强 MafA 和 Ngn3 诱导的 BNL CL.2 细胞向具有胰岛素分泌能力的β样细胞的重编程。并且，FIGF 的过表达增加了 BNL CL.2 细胞中 MafA 和 Ngn3 启动子区域组蛋白 H3/H4 乙酰化的水平。重要的是，研究进一步证实，FIGF 的强制表达促进了 STZ 小鼠胰岛素的表达并降低了其血糖水平。这些结果增强了通过利用非胰岛素分泌细胞来源的β样细胞来开发细胞治疗糖尿病的可能性。
