| First Author | Sehrawat A | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 15 | Pages | 4858-4869 |
| PubMed ID | 32122971 | Mgi Jnum | J:286822 |
| Mgi Id | MGI:6404675 | Doi | 10.1074/jbc.RA119.011011 |
| Citation | Sehrawat A, et al. (2020) SMAD7 enhances adult beta-cell proliferation without significantly affecting beta-cell function in mice. J Biol Chem 295(15):4858-4869 |
| abstractText | The interplay between the transforming growth factor beta (TGF-beta) signaling proteins, SMAD family member 2 (SMAD2) and 3 (SMAD3), and the TGF-beta-inhibiting SMAD, SMAD7, seems to play a vital role in proper pancreatic endocrine development and also in normal beta-cell function in adult pancreatic islets. Here, we generated conditional SMAD7 knockout mice by crossing insulin1(Cre) mice with SMAD7(fx/fx) mice. We also created a beta cell-specific SMAD7-overexpressing mouse line by crossing insulin1(Dre) mice with HPRT-SMAD7/RosaGFP mice. We analyzed beta-cell function in adult islets when SMAD7 was either absent or overexpressed in beta cells. Loss of SMAD7 in beta cells inhibited proliferation, and SMAD7 overexpression enhanced cell proliferation. However, alterations in basic glucose homeostasis were not detectable following either SMAD7 deletion or overexpression in beta cells. Our results show that both the absence and overexpression of SMAD7 affect TGF-beta signaling and modulates beta-cell proliferation but does not appear to alter beta-cell function. Reversible SMAD7 overexpression may represent an attractive therapeutic option to enhance beta-cell proliferation without negative effects on beta-cell function. |
