| First Author | El-Gohary Y | Year | 2014 |
| Journal | Diabetes | Volume | 63 |
| Issue | 1 | Pages | 224-36 |
| PubMed ID | 24089514 | Mgi Jnum | J:209044 |
| Mgi Id | MGI:5565582 | Doi | 10.2337/db13-0432 |
| Citation | El-Gohary Y, et al. (2014) A smad signaling network regulates islet cell proliferation. Diabetes 63(1):224-36 |
| abstractText | Pancreatic beta-cell loss and dysfunction are critical components of all types of diabetes. Human and rodent beta-cells are able to proliferate, and this proliferation is an important defense against the evolution and progression of diabetes. Transforming growth factor-beta (TGF-beta) signaling has been shown to affect beta-cell development, proliferation, and function, but beta-cell proliferation is thought to be the only source of new beta-cells in the adult. Recently, beta-cell dedifferentiation has been shown to be an important contributory mechanism to beta-cell failure. In this study, we tie together these two pathways by showing that a network of intracellular TGF-beta regulators, smads 7, 2, and 3, control beta-cell proliferation after beta-cell loss, and specifically, smad7 is necessary for that beta-cell proliferation. Importantly, this smad7-mediated proliferation appears to entail passing through a transient, nonpathologic dedifferentiation of beta-cells to a pancreatic polypeptide-fold hormone-positive state. TGF-beta receptor II appears to be a receptor important for controlling the status of the smad network in beta-cells. These studies should help our understanding of properly regulated beta-cell replication. |
