Investigation of the Molecular Mechanisms by Which Endothelin-3 Stimulates Preadipocyte Growth.
Front Endocrinol (Lausanne)
; 12: 661828, 2021.
Article
em En
| MEDLINE
| ID: mdl-34093437
ABSTRACT
Endothelins induce many biological responses, and they are composed of three peptides ET-1, ET-2, and ET-3. Reports have indicated that ET-1 regulates cell proliferation, adipogenesis, and other cell responses and that ET-3 stimulates the growth of gastrointestinal epithelial cells and melanocytes. However, the signalling pathways of ET3 that mediate the growth of fat cells are still unclear. Using 3T3-L1 white preadipocytes, we found that ET-3 induced increases in both cell number and BrdU incorporation. Pretreatment with an ETAR antagonist (but not an ETBR antagonist) blocked the ET-3-induced increases in both cell number and BrdU incorporation. Additionally, BQ610 suppressed the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3 proteins, and pretreatment with specific inhibitors of AMPK, JNK/c-JUN, or JAK/STAT3 prevented the ET-3-induced increases in phosphorylation of AMPK, c-JUN, and STAT3, respectively. Neither p38 MAPK inhibitor nor PKC inhibitor altered the effects of ET-3 on cell growth. These data suggest that ET-3 stimulates preadipocyte growth through the ETAR, AMPK, JNK/c-JUN, and STAT3 pathways. Moreover, ET-3 did not alter HIB1B brown preadipocyte and D12 beige preadipocyte growth, suggesting a preadipocyte type-dependent effect. The results of this study may help explain how endothelin mediates fat cell activity and fat cell-associated diseases.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Adipócitos
/
Endotelina-3
Limite:
Animals
Idioma:
En
Revista:
Front Endocrinol (Lausanne)
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Taiwan