Htr2b Promotes M1 Microglia Polarization and Neuroinflammation after Spinal Cord Injury via Inhibition of Neuregulin-1/ErbB Signaling

被引:6
作者
Chen, Wenhao [1 ,2 ]
Gao, Xianlei [1 ]
Yang, Wanliang [1 ,2 ]
Xiao, Xun [1 ,2 ]
Pan, Xin [1 ]
Li, Hao [1 ]
机构
[1] Shandong Univ, Dept Orthopaed, Qilu Hosp, Wenhuaxi Rd 107, Jinan 250012, Shandong, Peoples R China
[2] Shandong Univ, Cheeloo Coll Med, Jinan 250012, Shandong, Peoples R China
关键词
Spinal cord injury; Htr2b; Microglia; M1; polarization; Inflammation; ErbB signaling pathway; PATHWAY; TRANSPLANTATION; MACROPHAGES; ACTIVATION; THERAPIES; RECOVERY; NETWORK;
D O I
10.1007/s12035-023-03656-6
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The secondary injury of spinal cord injury (SCI) is dominated by neuroinflammation, which was caused by microglia M1 polarization. This study aimed to investigate the role and mechanism of Htr2b on neuroinflammation of SCI. The BV2 and HMC3 microglia were treated with lipopolysaccharide (LPS) or interferon (IFN)-& gamma; to simulate in vitro models of SCI. Sprague-Dawley rats were subjected to the T10 laminectomy to induce animal model of SCI. Htr2b mRNA expression was measured by qRT-PCR. The expression of Htr2b and Iba-1 was detected by western blot and immunofluorescence. The expression of inflammatory cytokines in vitro and in vivo was also measured. Kyoto Encyclopedia of Genes and Genomes (KEGG) was employed to analyze Htr2b-regulated signaling pathways. Rat behavior was analyzed by the Basso, Beattie, and Bresnahan (BBB) and inclined plane test. Rat dorsal horn tissues were stained by hematoxylin-eosin (H & E) and Nissl to measure neuron loss. Htr2b was highly expressed in LPS- and IFN-& gamma;-treated microglia and SCI rats. SCI modeling promoted M1 microglia polarization and increased levels of inflammatory cytokines. Inhibition of Htr2b by Htr2b shRNA or RS-127445 reduced the expression of Htr2b, Iba-1, and iNOS and suppressed cytokine levels. KEGG showed that Htr2b inhibited ErbB signaling pathway. Inhibition of Htr2b increased protein expression of neuregulin-1 (Nrg-1) and p-ErbB4. Inhibition of the ErbB signaling pathway markedly reversed the effect of Htr2b shRNA on M1 microglia polarization and inflammatory cytokines. Htr2b promotes M1 microglia polarization and neuroinflammation after SCI by inhibiting Nrg-1/ErbB signaling pathway.
引用
收藏
页码:1643 / 1654
页数:12
相关论文
共 52 条
[1]   Cell transplantation therapy for spinal cord injury [J].
Assinck, Peggy ;
Duncan, Greg J. ;
Hilton, Brett J. ;
Plemel, Jason R. ;
Tetzlaff, Wolfram .
NATURE NEUROSCIENCE, 2017, 20 (05) :637-647
[2]   A SENSITIVE AND RELIABLE LOCOMOTOR RATING-SCALE FOR OPEN-FIELD TESTING IN RATS [J].
BASSO, DM ;
BEATTIE, MS ;
BRESNAHAN, JC .
JOURNAL OF NEUROTRAUMA, 1995, 12 (01) :1-21
[3]   A population-specific HTR2B stop codon predisposes to severe impulsivity [J].
Bevilacqua, Laura ;
Doly, Stephane ;
Kaprio, Jaakko ;
Yuan, Qiaoping ;
Tikkanen, Roope ;
Paunio, Tiina ;
Zhou, Zhifeng ;
Wedenoja, Juho ;
Maroteaux, Luc ;
Diaz, Silvina ;
Belmer, Arnaud ;
Hodgkinson, Colin A. ;
Dell'Osso, Liliana ;
Suvisaari, Jaana ;
Coccaro, Emil ;
Rose, Richard J. ;
Peltonen, Leena ;
Virkkunen, Matti ;
Goldman, David .
NATURE, 2010, 468 (7327) :1061-U460
[4]   International surveillance study in acute spinal cord injury confirms viability of multinational clinical trials [J].
Bourguignon, Lucie ;
Tong, Bobo ;
Geisler, Fred ;
Schubert, Martin ;
Rohrich, Frank ;
Saur, Marion ;
Weidner, Norbert ;
Rupp, Rudiger ;
Kalke, Yorck-Bernhard B. ;
Abel, Rainer ;
Maier, Doris ;
Grassner, Lukas ;
Chhabra, Harvinder S. ;
Liebscher, Thomas ;
Cragg, Jacquelyn J. ;
Kramer, John ;
Curt, Armin ;
Jutzeler, Catherine R. .
BMC MEDICINE, 2022, 20 (01)
[5]   Microglia coordinate cellular interactions during spinal cord repair in mice [J].
Brennan, Faith H. ;
Li, Yang ;
Wang, Cankun ;
Ma, Anjun ;
Guo, Qi ;
Li, Yi ;
Pukos, Nicole ;
Campbell, Warren A. ;
Witcher, Kristina G. ;
Guan, Zhen ;
Kigerl, Kristina A. ;
Hall, Jodie C. E. ;
Godbout, Jonathan P. ;
Fischer, Andy J. ;
McTigue, Dana M. ;
He, Zhigang ;
Ma, Qin ;
Popovich, Phillip G. .
NATURE COMMUNICATIONS, 2022, 13 (01)
[6]   Microglia in Pain: Detrimental and Protective Roles in Pathogenesis and Resolution of Pain [J].
Chen, Gang ;
Zhang, Yu-Qiu ;
Qadri, Yawar J. ;
Serhan, Charles N. ;
Ji, Ru-Rong .
NEURON, 2018, 100 (06) :1292-1311
[7]   Inhibiting serotonin signaling through HTR2B in visceral adipose tissue improves obesity-related insulin resistance [J].
Choi, Won Gun ;
Choi, Wonsuk ;
Oh, Tae Jung ;
Cha, Hye-Na ;
Hwang, Inseon ;
Lee, Yun Kyung ;
Lee, Seung Yeon ;
Shin, Hyemi ;
Lim, Ajin ;
Ryu, Dongryeol ;
Suh, Jae Myoung ;
Park, So-Young ;
Choi, Sung Hee ;
Kim, Hail .
JOURNAL OF CLINICAL INVESTIGATION, 2021, 131 (23)
[8]   Spinal cord repair: advances in biology and technology [J].
Courtine, Gregoire ;
Sofroniew, Michael V. .
NATURE MEDICINE, 2019, 25 (06) :898-908
[9]   Emerging Roles of Microglia Depletion in the Treatment of Spinal Cord Injury [J].
Deng, Junhao ;
Meng, Fanqi ;
Zhang, Kexue ;
Gao, Jianpeng ;
Liu, Zhongyang ;
Li, Ming ;
Liu, Xiao ;
Li, Jiantao ;
Wang, Yu ;
Zhang, Licheng ;
Tang, Peifu .
CELLS, 2022, 11 (12)
[10]   Restoration of sensorimotor functions after spinal cord injury [J].
Dietz, Volker ;
Fouad, Karim .
BRAIN, 2014, 137 :654-667