Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis.
Int J Mol Sci
; 22(16)2021 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-34445177
ABSTRACT
Adipose tissues (AT) expand in response to energy surplus through adipocyte hypertrophy and hyperplasia. The latter, also known as adipogenesis, is a process by which multipotent precursors differentiate to form mature adipocytes. This process is directed by developmental cues that include members of the TGF-ß family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-ß family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-ß families, several ligand traps, and the SMAD1/5/8 signaling inhibitor LDN-193189 profoundly suppressed 3T3-L1 adipogenesis. Strikingly, anti-adipogenic traps and ligands engaged the same mechanism of action involving the simultaneous activation of SMAD2/3 and inhibition of SMAD1/5/8 signaling. This effect was rescued by the SMAD2/3 signaling inhibitor SB-431542. By contrast, although LDN-193189 also suppressed SMAD1/5/8 signaling and adipogenesis, its effect could not be rescued by SB-431542. Collectively, these findings reveal the fundamental role of SMAD1/5/8 for 3T3-L1 adipogenesis, and potentially identify a negative feedback loop that links SMAD2/3 activation with SMAD1/5/8 inhibition in adipogenic precursors.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Proteína Smad2
/
Proteína smad3
/
Adipogénesis
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Int J Mol Sci
Año:
2021
Tipo del documento:
Article