SESN3 Inhibited SMAD3 to Relieve Its Suppression for MiR-124, Thus Regulating Pre-Adipocyte Adipogenesis.

SESN3 Inhibited SMAD3 to Relieve Its Suppression for MiR-124, Thus Regulating Pre-Adipocyte Adipogenesis.
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SESN3 抑制 SMAD3 以解除其对 MiR-124 的抑制,从而调节前脂肪细胞脂肪生成

DOI:
10.3390/genes12121852
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发表时间:
2021-11-23
期刊:
影响因子:
3.5
通讯作者:
Chen J
Chen J
中科院分区:
生物学3区
文献类型:
--
作者:
Lin W;Zhao J;Yan M;Li X;Yang K;Wei W;Zhang L;Chen J

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Sestrin-3与另外两个成员Sestrin-1和Sestrin-2属于Sestrin家族。Sestrin蛋白家族已被证明参与抗氧化、代谢动态平衡,甚至参与非酒精性脂肪性肝炎(NASH)的发展。然而,SESN3在成脂过程中的成脂调控作用仍需进一步探讨。在这项研究中,我们证明了SESN3抑制猪前脂肪细胞的增殖,从而抑制其脂肪生成。同时,SESN3已被证明可以抑制SMAD3,从而保护NASH。此外,在我们之前的研究中,我们发现MMU-miR-124参与了3T3-L1细胞的脂肪生成调控。在本研究中,我们还发现SSC-miR-124抑制猪前脂肪细胞的增殖,从而抑制其成脂,Smad3是通过与其启动子结合而抑制SSC-miR-124的。此外,SSc-miR-124靶向猪C/EBPα和GR,从而抑制前脂肪细胞的脂肪生成。综上所述,SeSn3抑制Smad3,从而改善SSC-miR124,进而抑制C/EBPα和GR,从而调节前脂肪细胞的成脂。
Sestrin-3, together with the other two members Sestrin-1 and Sestrin-2, belongs to the Sestrin family. The Sestrin protein family has been demonstrated to be involved in antioxidative, metabolic homeostasis, and even the development of nonalcoholic steatohepatitis (NASH). However, the adipogenic regulatory role of SESN3 in adipogenesis still needs to be further explored. In this study, we demonstrated SESN3 inhibited porcine pre-adipocyte proliferation, thus suppressing its adipogenesis. Meanwhile, SESN3 has been demonstrated to inhibit Smad3 thus protecting against NASH. Further, for our previous study, we found mmu-miR-124 involved in 3T3-L1 cell adipogenesis regulation. In this study, we also identified that ssc-miR-124 inhibited porcine pre-adipocyte proliferation, thus suppressing its adipogenesis, and the SMAD3 was an inhibitor of ssc-miR-124 by binding to its promoter. Furthermore, the ssc-miR-124 targeted porcine C/EBPα and GR and thus inhibited pre-adipocyte adipogenesis. In conclusion, SESN3 inhibited SMAD3, thus improving ssc-miR124, and then suppressed C/EBPα and GR to regulate pre-adipocytes adipogenesis.
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