作者机构:
[梁瑜; 刘彦; 邹冬雪; 彭莉; 高勇强; 胡丽; 刘俊] Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hengyang 421001, China;[肖建华] Institute of Pathogenic Biology, Hengyang Medical School, University of South China, Hengyang 421001, China. *Corresponding author, E-mail: jhxiao223@163.com
作者机构:
[王紫涵; 何剑琴; 凌宏艳; 罗金定; 杨丝丝; 李梦伟] Hengyang Medical College, University of South China, Dept of Physiology,, Hunan, Hengyang, 421001, China;Physical Education Institute, Jishou University, Xiangxi, Hunan416000, China;[丁星星] Chuanshan College University of Sowth China, Hunan, 421001, China;[奉水东] Public Health College, University of South China.Hengyang, Dept of Social Medicine and Health Management,, Hunan, 421001, China;[Lyu H.-J.] Hengyang Medical College, University of South China, Dept of Physiology,, Hunan, Hengyang, 421001, China, Physical Education Institute, Jishou University, Xiangxi, Hunan416000, China
作者机构:
[邹聪; 蒋李平; 何云武; 肖振平] Second Affiliated Hospital of IS'anhua University, Dept of Fain and Rehabilitation, Hunan, Hengyang, 421003, China;School of Basic Medicine, A'Anhua University, Hunan, Hengyang, 421001, China;[龙慧] Second Affiliated Hospital of IS'anhua University, Dept of Fain and Rehabilitation, Hunan, Hengyang, 421003, China, School of Basic Medicine, A'Anhua University, Hunan, Hengyang, 421001, China
作者机构:
[邓芳] Department of Pathology, First Affiliated Hospital of University of South China, Hengyang, 421000, China;[刘思思; 谭华欣] Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hengyang Medical School, University of South China, Hengyang, 421000, China;[贺睿敏] Department of Radiotherapy, Second Affiliated Hospital of University of South China, Hengyang, 421000, China
通讯机构:
[Tan, H.] D;Department of Biochemistry and Molecular Biology, China
作者:
Yang Wu-Zhou;Li Heng;Yu Xiao-Hua;Zhang Jie;Huang Xin-Yun;...
期刊:
生物化学与生物物理进展,2022年49(2):401-412 ISSN:1000-3282
通讯作者:
Cao Qi;Tang, CK
作者机构:
[Li Heng; Cao Qi; Yang Wu-Zhou; Zhao Zhen-Wang; Zhang Jie; Tang Chao-Ke; Huang Xin-Yun] Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Affiliated Hosp 2,Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.;[Yu Xiao-Hua] Hainan Med Univ, Inst Clin Med, Affiliated Hosp 2, Haikou 460106, Peoples R China.
通讯机构:
[Cao, Q; Tang, CK ] U;Univ South China, Key Lab Arteriosclerol Hunan Prov, Hunan Prov Cooperat Innovat Ctr Mol Target New Dr, Affiliated Hosp 2,Inst Cardiovasc Dis, Hengyang 421001, Peoples R China.
关键词:
miR-216b;ABCG1
摘要:
Objective To investigated the function and the target gene of miR-216b in osteoclast differentiation and explored its effect on osteoclast cholesterol efflux.Methods The cell model of RAW264.7 osteoclast precursor cell differentiation induced by RANKL stimulation was established.Tartrate-resistant acid phosphatase(TRAP)staining assay was conducted to evaluate osteoclasts differentiation.MiR-216b target gene,ABCG1 3' untranslated region(3'UTR)sequence and free energy were predicted and analyzed by bioinformatics analyses and dual-luciferase reporter assays.MiR-216b mimic or inhibitor transfection was performed to verify the role of miR-216b in osteoclast differentiation.Liquid scintillation counting was used to measure [3H]-labeled cholesterol efflux from RAW264.7 macrophage-derived osteoclasts.The lipid accumulation in RAW264.7 macrophages was detected by high performance liquid chromatography(HPLC).Real-time quantitative PCR(RT-qPCR)and Western blot assays were used to assess the transcriptional and post-transcriptional levels of ABCG1 in osteoclasts.Results Our results showed that the number of osteoclasts,the average diameter of osteoclasts and the fusion index were significantly increased when cells were transfected with miR-216b mimic,as revealed by tartrate-resistant acid phosphatase-positive staining and microscopy assay.MiR-216b inhibitor showed the complete opposite outcome which brought additional evidence to our findings.Bioinformatics analysis and dualluciferase reporter assays showed that miR-216b targets the 3'UTR of ABCG1.Moreover,miR-216b suppressed both the mRNA and protein levels of ABCG1 in osteoclasts.Besides,we found that silencing of ABCG1 by ABCG1 siRNA increased the number of osteoclasts,the average diameter of osteoclasts and the fusion index.MiR-216b reduced cholesterol efflux from osteoclasts by inhibiting ABCG1 expression.Conclusion Collectively,these findings suggest that miR-216b downregulates ABCG1 expression and inhibits osteoclast cholesterol efflux,which disturbs cholesterol homeostasis and promotes osteoclastogenesis.
作者机构:
[陈娟; 贺秋冬] Department of Radiotherapy, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, Hengyang, 421001, China;[蒋斌] Department of Plastic Surgery, The Second Affiliated Hospital, Hengyang Medical School, University of South China, Hunan, Hengyang, 421001, China;[黄果] Cancer Research Institute, Hengyang Medical School, University of South China, Hunan, Hengyang, 421001, China
通讯机构:
[Jiang, B.] D;Department of Plastic Surgery, Hunan, China
作者机构:
[Peng, Zhixin; Yuan, Zengqiang] Univ South China, Hengyang Med Coll, Inst Neurosci, Hengyang 421001, Peoples R China.;[Li, Xiaoheng; Gao, Yuhao; Peng, Zhixin; Yuan, Zengqiang] Beijing Inst Basic Med Sci, Brain Sci Ctr, 27 Taiping Rd, Beijing 100850, Peoples R China.;[Li, Jun] Capital Med Univ, Beijing Inst Brain Disorders, Beijing 100069, Peoples R China.;[Dong, Yuan] Qingdao Univ, Inst Brain Sci & Dis, Coll Med, Qingdao 266071, Peoples R China.;[Yan, Meichen; Yuan, Zengqiang; Cheng, Jinbo; Liao, Yajin] Minzu Univ China, Coll Life & Environm Sci, Ctr Translat Neurosci, Beijing 100081, Peoples R China.
通讯机构:
[Yuan, Zengqiang] I;[Cheng, Jinbo] C;Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang, 421001, China.;The Brain Science Center, Beijing Institute of Basic Medical Sciences, 27 Taiping Road, Haidian District, Beijing, 100850, China.;Center on Translational Neuroscience, College of Life and Environmental Science, Minzu University of China, Beijing, 100081, China.
关键词:
Dlg1;Microglia;Neuroinflammation;Depression
摘要:
Microglia-mediated neuroinflammation is widely perceived as a contributor to numerous neurological diseases and mental disorders including depression. Discs large homolog 1 (Dlg1), an adaptor protein, regulates cell polarization and the function of K+ channels, which are reported to regulate the activation of microglia. However, little is known about the role of Dlg1 in microglia and the maintenance of central nervous system homeostasis. In this study, we found that Dlg1 knockdown suppressed lipopolysaccharide (LPS)-induced inflammation by down-regulating the activation of nuclearfactor-κB signaling and the mitogen-activated protein kinase pathway in microglia. Moreover, using an inducible Dlg1 microglia-specific knockout (Dlg1flox/flox; CX3CR1CreER) mouse line, we found that microglial Dlg1 knockout reduced the activation of microglia and alleviated the LPS-induced depression-like behavior. In summary, our results demonstrated that Dlg1 plays a critical role in microglial activation and thus provides a potential therapeutic target for the clinical treatment of depression.
作者机构:
[Tao W.; Jian H.; Yongdong L.; Yonghong D.; Yuanding J.; Peng X.; Richu L.] Department of Neurosurgery, Second Hospital Affiliated to University of South China, Hengyang, 421001, China;[Yongmei Y.] Department of Anatomy, Medical School, University of South China, Hengyang, 421001, China
通讯机构:
[Yongmei, Y.] D;Department of Anatomy, China
摘要:
Microglia-associated neuroinflammation plays an important role in the pathophysiology of ischemic stroke. Microglial activation and polarization, and the inflammatory response mediated by these cells play important roles in the development, progression and outcome of brain injury after ischemic stroke. Currently, there is no effective strategy for treating ischemic stroke in clinical practice. Therefore, it is clinically important to study the role and regulation of microglia in stroke. In this review, we discuss the involvement of microglia in the neuroinflammatory process in ischemic stroke, with the aim of providing a better understanding of the relationship between ischemic stroke and microglia.