title: TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression.
abstract: Proliferation of pancreatic β-cells is an important mechanism underlying β-cell mass adaptation to metabolic demands. Increasing β-cell mass by regeneration may ameliorate or correct both type 1 and type 2 diabetes, which both result from inadequate production of insulin by β-cells of the pancreatic islet. Transforming growth factor β (TGF-β) signaling is essential for fetal development and growth of pancreatic islets. In this study, we exposed HIT-T15, a clonal pancreatic β-cell line, to TGF-β signaling. We found that inhibition of TGF-β signaling promotes proliferation of the cells significantly, while TGF-β signaling stimulation inhibits proliferation of the cells remarkably. We confirmed that this proliferative regulation by TGF-β signaling is due to the changed expression of the cell cycle regulator p27. Furthermore, we demonstrated that there is no observed effect on transcriptional activity of p27 by TGF-β signaling. Our data show that TGF-β signaling mediates the cell-cycle progression of pancreatic β-cells by regulating the nuclear localization of CDK inhibitor, p27. Inhibition of TGF-β signaling reduces the nuclear accumulation of p27, and as a result this inhibition promotes proliferation of β-cells.
authors.affiliation: Department of Pathology and Cell Regulation, Kyoto Prefectural University of Medicine ; Department of Transplantation and Regenerative Surgery, Kyoto Prefectural University of Medicine.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Suzuki
authors.forename: Ping
authors.initials: P
authors.lastname: Dai
authors.forename: Tomoya
authors.initials: T
authors.lastname: Hatakeyama
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Harada
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Norio
authors.initials: N
authors.lastname: Yoshimura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takamatsu
keywords: HIT-T15 cells; TGF-β signaling; inhibition; p27; pancreatic β-cell proliferation