Back to Search
Start Over
SMAD7 enhances adult β-cell proliferation without significantly affecting β-cell function in mice.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2020 Apr 10; Vol. 295 (15), pp. 4858-4869. Date of Electronic Publication: 2020 Mar 02. - Publication Year :
- 2020
-
Abstract
- The interplay between the transforming growth factor β (TGF-β) signaling proteins, SMAD family member 2 (SMAD2) and 3 (SMAD3), and the TGF-β-inhibiting SMAD, SMAD7, seems to play a vital role in proper pancreatic endocrine development and also in normal β-cell function in adult pancreatic islets. Here, we generated conditional SMAD7 knockout mice by crossing insulin1 <superscript>Cre</superscript> mice with SMAD7 <superscript>fx/fx</superscript> mice. We also created a β cell-specific SMAD7-overexpressing mouse line by crossing insulin1 <superscript>Dre</superscript> mice with HPRT-SMAD7/RosaGFP mice. We analyzed β-cell function in adult islets when SMAD7 was either absent or overexpressed in β cells. Loss of SMAD7 in β 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 β cells. Our results show that both the absence and overexpression of SMAD7 affect TGF-β signaling and modulates β-cell proliferation but does not appear to alter β-cell function. Reversible SMAD7 overexpression may represent an attractive therapeutic option to enhance β-cell proliferation without negative effects on β-cell function.<br /> (© 2020 Sehrawat et al.)
- Subjects :
- Animals
Female
Glucose pharmacology
Male
Mice
Mice, Knockout
Signal Transduction
Sweetening Agents pharmacology
Transforming Growth Factor beta genetics
Cell Proliferation
Insulin physiology
Insulin Secretion drug effects
Insulin-Secreting Cells cytology
Insulin-Secreting Cells physiology
Smad7 Protein physiology
Transforming Growth Factor beta metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 295
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32122971
- Full Text :
- https://doi.org/10.1074/jbc.RA119.011011