Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine

doi:10.1007/s13167-024-00394-0

科研成果详情

题名	Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine
作者	Tao, Guorong 1,2,3,4; Wang, Xuebao5; Wang, Jian2,3,6; Ye, Yiru2,3,7; Zhang, Minxue1,2,3; Lang, Yan1,2,3; Ding, Saidan1,2,3
发表日期	2025-01-10
发表期刊	EPMA JOURNAL 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	Predictive preventive personalized medicine (PPPM / 3PM) Diabetic encephalopathy (DE) Early risk prediction Morris water maze test Y-maze test SP2(-/-) mice Streptozocin-treated mice Db/db mice Primary cultured hippocampal neurons N2A cells Nerve damage Neuroinflammation Oxidative stress Specificity Protein 2 (SP2) X-box binding protein 1 (XBP1)
其他关键词	NF-KAPPA-B ; BOX-BINDING PROTEIN-1 ; TRANSCRIPTION FACTOR XBP1 ; INSULIN-RESISTANCE ; HEME OXYGENASE-1 ; GENETIC RISK ; ER STRESS ; NRF2 ; ACTIVATION ; SP2
摘要	Background Transcription factor specificity protein (SP2) regulates various cellular functions, including cell division, proliferation, invasion, metastasis, differentiation, and death; however, its role has not been studied in prominent medical conditions including diabetic encephalopathy (DE). Therefore, this study addressed its physiological function in the context of DE to also better characterize its possible use in the context of predictive, preventive, and personalized medicine (PPPM). Methods The anti-inflammatory and anti-DE actions of SP2 were investigated using three animal models (SP2(-/-) mice, streptozocin-treated mice, and db/db mice) and two cell lines (primary cultured hippocampal neurons and N2A cells). The db/db mice were a leptin deficiency model often used to study type 2 diabetes. An equal number of males and females (8-12 weeks of age) was selected. Behavioral changes in mice were determined using both morris water maze (MWM) test and Y-maze (YM) test. The alterations in oxidative stress and inflammation were examined via immunofluorescence assay, flow cytometry, co-immunoprecipitation, and immunoblotting. Results Mechanistically, SP2-knockout (SP2(-/-)) mice showed dysregulation of insulin/glucose homeostasis, neuroinflammation, and cognitive loss. Otherwise, in db/db DE mice and STZ-induced DE mice, neuroinflammation, neuroapoptosis, and cognitive decline were significantly attenuated when SP2 was overexpressed in the brain. On the other hand, SP2 overexpression activates the insulin signaling pathway and improves insulin resistance via targeting X-box binding protein 1 (XBP1) in neurons. Moreover, SP2 overexpression significantly reduces oxidative stress by interacting with XBP1 and nuclear factor erythroid 2-related factor 2 (NRF2) in neurons. Furthermore, SP2 enhances the suppression of inflammatory response triggered by nuclear factor kappa B (NF kappa B) through the recruitment of XBP1 and NRF2 and by the in vitro inactivation of I kappa B kinase (IKK) complex. Conclusions These findings highlight SP2 as key biological targets for DE and reveal the infammation-related potential molecular mechanism of DE, which is helpful for early risk prediction and targeted prevention of DE. In conclusion, our study provides a new perspective for developing a PPPM method for managing DE patients.
资助项目	Natural Science Foundation of China .
出版者	SPRINGER INT PUBL AG
ISSN	1878-5077
EISSN	1878-5085
DOI	10.1007/s13167-024-00394-0
页数	27
WOS类目	Medicine, General & Internal ; Medicine, Research & Experimental
WOS研究方向	General & Internal Medicine ; Research & Experimental Medicine
WOS记录号	WOS:001395302300001
收录类别	SCIE
通讯作者地址	[Ding, Saidan]Fudan Univ, Lab Anim Ctr, Shanghai 200032, Peoples R China. ; [Ding, Saidan]Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Dis, Wenzhou 325000, Peoples R China. ; [Ding, Saidan]Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou 325000, Zhejiang, Peoples R China.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/224866
专题	附属第一医院药学院（分析测试中心）第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
通讯作者	Ding, Saidan
作者单位	1.Fudan Univ, Lab Anim Ctr, Shanghai 200032, Peoples R China; 2.Wenzhou Med Univ, Affiliated Hosp 1, Key Lab Diag & Treatment Severe Hepatopancreat Dis, Wenzhou 325000, Peoples R China; 3.Wenzhou Med Univ, Affiliated Hosp 1, Cent Lab, Wenzhou 325000, Zhejiang, Peoples R China; 4.Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Anesthesiol, Shanghai 200025, Peoples R China; 5.Wenzhou Med Univ, Sch Pharmaceut Sci, Wenzhou 325000, Zhejiang, Peoples R China; 6.Hubei Polytech Univ, Huangshi Love & Hlth Hosp, Huangshi 435000, Peoples R China; 7.Wenzhou Med Univ, Sch Informat & Engn, Wenzhou 325035, Zhejiang, Peoples R China
第一作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
通讯作者单位	附属第一医院; 第一临床医学院（信息与工程学院）、附属第一医院_中心实验室
推荐引用方式 GB/T 7714	Tao, Guorong,Wang, Xuebao,Wang, Jian,et al. Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine[J]. EPMA JOURNAL,2025.
APA	Tao, Guorong., Wang, Xuebao., Wang, Jian., Ye, Yiru., Zhang, Minxue., ... & Ding, Saidan. (2025). Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine. EPMA JOURNAL.
MLA	Tao, Guorong,et al."Identifying Specificity Protein 2 as a key marker for diabetic encephalopathy in the context of predictive, preventive, and personalized medicine".EPMA JOURNAL (2025).