Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation.
Glycoprotein M6B Interacts with TβRI to Activate TGF-β-Smad2/3 Signaling and Promote Smooth Muscle Cell Differentiation.
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糖蛋白 M6B 与 TβRI 相互作用，激活 TGF-β-Smad2/3 信号传导并促进平滑肌细胞分化。
DOI：
10.1002/stem.2938
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Tao L
中科院分区：
文献类型：
--
作者：
Zhang X;Xie H;Chang P;Zhao H;Xia Y;Zhang L;Guo X;Huang C;Yan F;Hu L;Lin C;Li Y;Xiong Z;Wang X;Li G;Deng L;Wang S;Tao L
形成血管壁的平滑肌细胞（SMC）在血管发育和血管重塑的致病过程中发挥着重要作用。然而，控制 SMC 分化的分子机制仍然知之甚少。糖蛋白 M6B (GPM6B) 是一种四跨膜蛋白，属于蛋白脂质蛋白家族，广泛表达于神经元、少突胶质细胞和星形胶质细胞中。先前的研究表明，GPM6B 在神经元分化、髓鞘形成和成骨细胞分化中发挥作用。在本研究中，我们发现在转化生长因子-β1（TGF-β1）诱导的 SMC 分化过程中，GPM6B 基因和蛋白表达水平显着上调。 GPM6B 的敲低导致 SMC 特异性标记物表达下调，并抑制 Smad2/3 信号传导的激活。此外，GPM6B 通过控制 TGF-β-Smad2/3 信号传导来调节 SMC 分化。此外，我们证明与 p-Smad2/3 类似，GPM6B 在胚胎 SMC 中深度表达并与 SMC 分化标记物共表达。此外，GPM6B可以通过直接与TβRI结合来调节TβRI、TβRII或Smad2/3之间的紧密度，从而在SMC分化过程中激活Smad2/3信号，并且TGF-β-Smad2/3信号的激活也促进GPM6B的表达。总而言之，这些发现表明 GPM6B 在 SMC 分化中发挥着至关重要的作用，并通过与 TβRI 直接相互作用激活 TGF-β-Smad2/3 信号传导来调节 SMC 分化。这一发现表明，GPM6B 是心血管再生医学中从干细胞衍生 SMC 的潜在靶点。干细胞 2018 干细胞 2019;37:190–201 总之，本研究表明 GPM6B 在 SMC 分化中发挥着至关重要的作用。 GPM6B通过调节TβRI与TβRII或Smad2/3之间的紧密度，激活TGF-β-Smad2/3信号传导来促进SMC分化，而TGF-β-Smad2/3信号传导的激活也促进GPM6B的表达。
Smooth muscle cells (SMCs), which form the walls of blood vessels, play an important role in vascular development and the pathogenic process of vascular remodeling. However, the molecular mechanisms governing SMC differentiation remain poorly understood. Glycoprotein M6B (GPM6B) is a four‐transmembrane protein that belongs to the proteolipid protein family and is widely expressed in neurons, oligodendrocytes, and astrocytes. Previous studies have revealed that GPM6B plays a role in neuronal differentiation, myelination, and osteoblast differentiation. In the present study, we found that the GPM6B gene and protein expression levels were significantly upregulated during transforming growth factor‐β1 (TGF‐β1)‐induced SMC differentiation. The knockdown of GPM6B resulted in the downregulation of SMC‐specific marker expression and repressed the activation of Smad2/3 signaling. Moreover, GPM6B regulates SMC Differentiation by Controlling TGF‐β‐Smad2/3 Signaling. Furthermore, we demonstrated that similar to p‐Smad2/3, GPM6B was profoundly expressed and coexpressed with SMC differentiation markers in embryonic SMCs. Moreover, GPM6B can regulate the tightness between TβRI, TβRII, or Smad2/3 by directly binding to TβRI to activate Smad2/3 signaling during SMC differentiation, and activation of TGF‐β‐Smad2/3 signaling also facilitate the expression of GPM6B. Taken together, these findings demonstrate that GPM6B plays a crucial role in SMC differentiation and regulates SMC differentiation through the activation of TGF‐β‐Smad2/3 signaling via direct interactions with TβRI. This finding indicates that GPM6B is a potential target for deriving SMCs from stem cells in cardiovascular regenerative medicine. stem cells 2018 Stem Cells 2019;37:190–201 In summary, the present study revealed that GPM6B play a crucial role in SMC differentiation. GPM6B promotes SMC differentiation through the activation of TGF‐β‐Smad2/3 signaling via regulating the tightness between TβRI and TβRII or Smad2/3 by directly binding to TβRI to activate Smad2/3 signaling, and activation of TGF‐β‐Smad2/3 signaling also facilitate the expression of GPM6B.
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影响因子：
3.5
作者：
Cai, Yu;Zhou, Chao Hui;Shen, Xi Zhong
通讯作者：
Shen, Xi Zhong
DOI：
10.1074/jbc.ra118.001739
发表时间：
2018-05-25
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Gu W;Hong X;Le Bras A;Nowak WN;Issa Bhaloo S;Deng J;Xie Y;Hu Y;Ruan XZ;Xu Q
通讯作者：
Xu Q
影响因子：
6.2
作者：
Drabek, Ksenija;van de Peppel, Jeroen;van Leeuwen, Johannes P. T. M.
通讯作者：
van Leeuwen, Johannes P. T. M.
影响因子：
4.8
作者：
Ghionzoli, Marco;Repele, Andrea;De Coppi, Paolo
通讯作者：
De Coppi, Paolo
影响因子：
4.8
作者：
Hao, Xinbao;Wang, Yinyin;Chang, Zhijie
通讯作者：
Chang, Zhijie