SMAD7 enhances adult ß-cell proliferation without significantly affecting ß-cell function in mice.
J Biol Chem
; 295(15): 4858-4869, 2020 04 10.
Article
in En
| MEDLINE
| ID: mdl-32122971
ABSTRACT
The interplay between the transforming growth factor ß (TGF-ß) signaling proteins, SMAD family member 2 (SMAD2) and 3 (SMAD3), and the TGF-ß-inhibiting SMAD, SMAD7, seems to play a vital role in proper pancreatic endocrine development and also in normal ß-cell function in adult pancreatic islets. Here, we generated conditional SMAD7 knockout mice by crossing insulin1Cre mice with SMAD7fx/fx mice. We also created a ß cell-specific SMAD7-overexpressing mouse line by crossing insulin1Dre mice with HPRT-SMAD7/RosaGFP mice. We analyzed ß-cell function in adult islets when SMAD7 was either absent or overexpressed in ß cells. Loss of SMAD7 in ß 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 ß cells. Our results show that both the absence and overexpression of SMAD7 affect TGF-ß signaling and modulates ß-cell proliferation but does not appear to alter ß-cell function. Reversible SMAD7 overexpression may represent an attractive therapeutic option to enhance ß-cell proliferation without negative effects on ß-cell function.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Transforming Growth Factor beta
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Cell Proliferation
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Insulin-Secreting Cells
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Smad7 Protein
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Insulin Secretion
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Insulin
Limits:
Animals
Language:
En
Journal:
J Biol Chem
Year:
2020
Document type:
Article