Inhibition of vascular adventitial remodeling by netrin-1 in diabetic rats.
Inhibition of vascular adventitial remodeling by netrin-1 in diabetic rats.
复制标题
Netrin-1 对糖尿病大鼠血管外膜重塑的抑制作用。
DOI：
10.1530/joe-19-0258
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发表时间：
2019-12
影响因子：
4
通讯作者：
Xu Ming
中科院分区：
文献类型：
--
作者：
Wang Hui-Fang;Yu Qing-Qing;Zheng Rui-Fang;Xu Ming
Cardiovascular complications of type 2 diabetes mellitus (T2DM) are associated with vascular remodeling in the arteries. Perivascular sympathetic neurons release an abundance of trophic factors to regulate vascular function via a paracrine signaling. Netrin-1, a diffusible protein that can be secreted outside the cell, is one of common signals of 'conversation' between nerve and vessel. The present study investigated whether netrin-1 is a novel modulator of sympathetic neurons paracrine signaling and played a critical role in vascular adventitial remodeling under T2DM. Vascular adventitial remodeling was observed in adventitial fibroblasts (AFs) responding to netrin-1 deficiency in the supernatant from primary rat superior cervical ganglia (SCG) neurons, shown as AFs proliferation, migration, and collagen deposition. Conditioned medium from the high glucose (HG)-treated SCG neurons contributed to AFs remodeling, which was effectively alleviated by exogenous netrin-1 supplementation. Further, it was found that uncoordinated-5-B (UNC5b) was mainly expressed in AFs among netrin-1 specific receptors. Treatment of netrin-1 inhibited H2O2 production derived from NADPH oxidase 4 (Nox4) through the UNC5b/cAMP/PKA signal pathway in AFs remodeling. In vivo, aorta adventitial remodeling was accompanied with the down-regulation of netrin-1 in the perivascular sympathetic nerve in T2DM rats. Such abnormalities were restored by netrin-1 intervention, which was associated with the inhibition of Nox4 expression in the aorta adventitia. In conclusion, netrin-1 is a novel modulator of sympathetic neurons paracrine signaling to maintain AFs function. Vascular adventitial remodeling was aggravated by sympathetic neurons paracrine signaling under hyperglycemia, which was ameliorated by netrin-1 treatment through the UNC5b/cAMP/PKA/Nox4 pathway.
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影响因子：
4.2
作者：
Ranganathan P;Mohamed R;Jayakumar C;Brands MW;Ramesh G
通讯作者：
Ramesh G
影响因子：
11.4
作者：
Prior, Kim-Kristin;Leisegang, Matthias S.;Josipovic, Ivana;Loewe, Oliver;Shah, Ajay M.;Weissmann, Norbert;Schroeder, Katrin;Brandes, Ralf P.
通讯作者：
Brandes, Ralf P.
DOI：
10.1016/s1357-2725(96)00084-2
发表时间：
1996
期刊：
The international journal of biochemistry & cell biology
影响因子：
--
作者：
K. P. Shatwell;A. Segal
通讯作者：
K. P. Shatwell;A. Segal
影响因子：
7
作者：
B. Babior
通讯作者：
B. Babior
影响因子：
4.2
作者：
Bumstock, Geoffrey
通讯作者：
Bumstock, Geoffrey