TGF-β Signaling Regulates Pancreatic β-Cell Proliferation through Control of Cell Cycle Regulator p27 Expression

• Published in: ACTA HISTOCHEMICA ET CYTOCHEMICA Vol. 46; no. 2; pp. 51 - 58
• Main Authors: Suzuki, Tomoyuki, Dai, Ping, Hatakeyama, Tomoya, Harada, Yoshinori, Tanaka, Hideo, Yoshimura, Norio, Takamatsu, Tetsuro
• Format: Journal Article
• Language: English
• Published: Japan JAPAN SOCIETY OF HISTOCHEMISTRY AND CYTOCHEMISTRY 01.01.2013; Japan Society of Histochemistry and Cytochemistry
• Subjects: HIT-T15 cells; inhibition; p27; pancreatic β-cell proliferation; Regular; TGF-β signaling; inhibition; HIT-T15 cells; p27; TGF-β signaling; pancreatic β-cell proliferation
• ISSN: 0044-5991; 1347-5800
• DOI: 10.1267/ahc.12035

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.