Inhibition of TGF-β Signaling Promotes Human Pancreatic β-Cell Replication

• DOI: 10.2337/db15-1331
• Publication Date: 2016-03-03T03:53:31Z
• Authors: Sangeeta Dhawan; Ercument Dirice; Rohit N. Kulkarni; Anil Bhushan
• Keywords: Pancreatic Islets; Cell Signaling

Diabetes is associated with loss of functional pancreatic β-cells, and restoration β-cells a major goal for regenerative therapies. Endogenous regeneration via β-cell replication has the potential to restore cellular mass; however, pharmacological agents that promote or expansion endogenous have been elusive. The capacity declines rapidly age, due accumulation p16INK4a, resulting in limited adult endocrine pancreas regeneration. Here, we show transforming growth factor-β (TGF-β) signaling Smad3 integrates trithorax complex activate maintain Ink4a expression prevent replication. Importantly, inhibition TGF-β can result repression Ink4a/Arf locus, increased mice. Furthermore, small molecule inhibitors pathway human islets transplanted into NOD-scid IL-2Rgnull These data reveal novel role regulation locus highlight using