Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis.
Smad2/3 Activation Regulates Smad1/5/8 Signaling via a Negative Feedback Loop to Inhibit 3T3-L1 Adipogenesis.
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Smad 2/3激活通过负反馈环调节Smad 1/5/8信号通路抑制3 T3-L1脂肪生成
DOI：
10.3390/ijms22168472
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发表时间：
2021-08-06
影响因子：
5.6
通讯作者：
Martinez-Hackert E
中科院分区：
文献类型：
--
作者：
Aykul S;Maust J;Thamilselvan V;Floer M;Martinez-Hackert E
脂肪组织(AT)通过脂肪细胞肥大和增殖来响应能量过剩而扩张。后者，也被称为脂肪生成，是多潜能前体细胞分化形成成熟脂肪细胞的过程。这一过程是由包括转化生长因子-β家族成员在内的发育线索指导的。我们的目标是利用3T3-L1成脂模型阐明转化生长因子-β家族生长因子和抑制物如何调控脂肪细胞的发育。我们发现激活素和转化生长因子-β家族的配体、几个配体陷阱和Smad1/5/8信号抑制剂LDN-193189深刻地抑制了3T3-L1的成脂。值得注意的是，抗成脂陷阱和配体参与了相同的作用机制，包括同时激活Smad2/3和抑制Smad1/5/8信号。这种作用被Smad2/3信号抑制剂SB-431542所挽救。相反，尽管Ldn-193189也抑制Smad1/5/8信号转导和脂肪形成，但其作用不能被Sb-431542所挽救。总之，这些发现揭示了Smad1/5/8在3T3-L1脂肪形成中的基础作用，并可能识别出在成脂前体中将Smad2/3激活与Smad1/5/8抑制联系起来的负反馈环路。
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-β family. Our goal here was to elucidate, using the 3T3-L1 adipogenesis model, how TGF-β family growth factors and inhibitors regulate adipocyte development. We show that ligands of the Activin and TGF-β 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.
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影响因子：
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作者：
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通讯作者：
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10.1161/atvbaha.114.303034
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