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

ABSTRACT

Limitation in the number of insulin-producing pancreatic b-cells is a typical feature of diabetes. It has been indicated thatactivating pancreatic transcription factors can promote the transformation of hepatocytes into insulin-secreting b-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 observedthat treatment with Ad-FIGF was found to enhance MafA and Ngn3-induced reprogramming of BNL CL.2 cells to b-likecells with the ability of secreting insulin. And FIGF overexpression increased the levels of histone H3/H4 acetylation atMafA and Ngn3 promoter regions in BNL CL.2 cells. Importantly, in vivo study further confirmed that forced expression ofFIGF facilitated the insulin expression and decreased the blood glucose levels in STZ mice. These results strengthen thepossibility of developing cell-based therapies for diabetes through utilizing b-like cells derived from non-insulin-secretingcells.