Met-Controlled Allosteric Module of Neural Generation as A New Therapeutic Target in Rodent Brain Ischemia.
10.1007/s11655-019-3182-8
- Author:
Kang-Ning LI
1
;
Ying-Ying ZHANG
2
;
Ya-Nan YU
2
;
Hong-Li WU
2
;
Zhong WANG
3
Author Information
1. Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100070, China.
2. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China.
3. Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China. zhonw@vip.sina.com.
- Publication Type:Journal Article
- Keywords:
Inppl1-Met-Dapk3;
allosteric module;
brain ischemia;
generation of neurons
- MeSH:
Animals;
Brain Ischemia/drug therapy*;
Gene Ontology;
Gene Regulatory Networks;
Rodentia;
Vascular Endothelial Growth Factor A
- From:
Chinese journal of integrative medicine
2021;27(12):896-904
- CountryChina
- Language:English
-
Abstract:
OBJECTIVE:To investigate a Met-controlled allosteric module (AM) of neural generation as a potential therapeutic target for brain ischemia.
METHODS:We selected Markov clustering algorithm (MCL) to mine functional modules in the related target networks. According to the topological similarity, one functional module was predicted in the modules of baicalin (BA), jasminoidin (JA), cholic acid (CA), compared with I/R model modules. This functional module included three genes: Inppl1, Met and Dapk3 (IMD). By gene ontology enrichment analysis, biological process related to this functional module was obtained. This functional module participated in generation of neurons. Western blotting was applied to present the compound-dependent regulation of IMD. Co-immunoprecipitation was used to reveal the relationship among the three members. We used IF to determine the number of newborn neurons between compound treatment group and ischemia/reperfusion group. The expressions of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 9 (MMP-9) were supposed to show the changing circumstances for neural generation under cerebral ischemia.
RESULTS:Significant reduction in infarction volume and pathological changes were shown in the compound treatment groups compared with the I/R model group (P<0.05). Three nodes in one novel module of IMD were found to exert diverse compound-dependent ischemic-specific excitatory regulatory activities. An anti-ischemic excitatory allosteric module (AM
CONCLUSIONS:AM
