Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells.

Neuropilin 1 (NRP1) Positively Regulates Adipogenic Differentiation in C3H10T1/2 Cells.
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神经纤毛蛋白1(NRP 1)对C3 H10 T1/2细胞成脂分化的正调控作用

DOI:
10.3390/ijms24087394
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发表时间:
2023-04-17
影响因子:
5.6
通讯作者:
Qiu, Lihong
Qiu, Lihong
中科院分区:
生物学2区
文献类型:
--
作者:
Yu, Yaqiong;Uchida-Fukuhara, Yoko;Weng, Yao;He, Yuhan;Ikegame, Mika;Wang, Ziyi;Yoshida, Kaya;Okamura, Hirohiko;Qiu, Lihong

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神经粘蛋白1(Nrp1)是一种多种配体的非酪氨酸激酶受体,在多种间充质干细胞(MSCs)中均有高表达,但对其功能知之甚少。在这项研究中,我们探索了全长Nrp1和糖胺多聚糖(GAG)可修饰的Nrp1在C3H10T1/2细胞脂肪形成中的作用。在C3H10T1/2细胞成脂分化过程中,全长Nrp1和可修饰GAG的Nrp1表达增加。Nrp1基因敲除抑制脂肪形成,同时降低Akt和ERK1/2的磷酸化水平。此外,支架蛋白JIP4通过与Nrp1相互作用参与了C3H10T1/2细胞的成脂过程。此外,非GAG修饰的Nrp1突变体(S612A)的过表达显著促进了成脂分化,并伴随着磷酸化Akt和ERK1/2的上调。综上所述,这些结果表明Nrp1是一个关键的调控因子,通过与JIP4相互作用并激活Akt和ERK1/2途径促进C3H10T1/2细胞的成脂。非GAG修饰的Nrp1突变体(S612A)加速了成脂分化过程,提示GAG糖基化是Nrp1在成脂分化过程中的负翻译后修饰。
Neuropilin 1 (NRP1), a non-tyrosine kinase receptor for several ligands, is highly expressed in many kinds of mesenchymal stem cells (MSCs), but its function is poorly understood. In this study, we explored the roles of full-length NRP1 and glycosaminoglycan (GAG)-modifiable NRP1 in adipogenesis in C3H10T1/2 cells. The expression of full-length NRP1 and GAG-modifiable NRP1 increased during adipogenic differentiation in C3H10T1/2 cells. NRP1 knockdown repressed adipogenesis while decreasing the levels of Akt and ERK1/2 phosphorylation. Moreover, the scaffold protein JIP4 was involved in adipogenesis in C3H10T1/2 cells by interacting with NRP1. Furthermore, overexpression of non-GAG-modifiable NRP1 mutant (S612A) greatly promoted adipogenic differentiation, accompanied by upregulation of the phosphorylated Akt and ERK1/2. Taken together, these results indicate that NRP1 is a key regulator that promotes adipogenesis in C3H10T1/2 cells by interacting with JIP4 and activating the Akt and ERK1/2 pathway. Non-GAG-modifiable NRP1 mutant (S612A) accelerates the process of adipogenic differentiation, suggesting that GAG glycosylation is a negative post-translational modification of NRP1 in adipogenic differentiation.
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