2. Academic Validation
  3. HMGB1 Promotes the Release of Sonic Hedgehog From Astrocytes

HMGB1 Promotes the Release of Sonic Hedgehog From Astrocytes

  • Front Immunol. 2021 Apr 1;12:584097. doi: 10.3389/fimmu.2021.584097.
Yifan Xiao 1 2 3,  Yan Sun 4 5,  Wei Liu 1 3,  FanFan Zeng 2,  Junyu Shi 2,  Jun Li 2,  Huoying Chen 6,  Chang Tu 7,  Yong Xu 2,  Zheng Tan 2,  Feili Gong 2,  Xiji Shu 1 3,  Fang Zheng 2 8
Affiliations

Affiliations

  • 1 Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, China.
  • 2 Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 3 School of Medicine, Institutes of Biomedical Sciences, Jianghan University, Wuhan, China.
  • 4 Wuhan Institute for Neuroscience and Neuroengineering, South-Central University for Nationalities, Wuhan, China.
  • 5 Department of Neurobiology, College of Life Sciences, South-Central University for Nationalities, Wuhan, China.
  • 6 Department of Laboratory Medicine, The Second Affiliated Hospital of Guilin Medical University, Guilin, China.
  • 7 Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan, China.
  • 8 Key Laboratory of Organ Transplantation, Ministry of Education, NHC Key Laboratory of Organ Transplantation, Key Laboratory of Organ Transplantation, Chinese Academy of Medical Sciences, Wuhan, China.
PMID: 33868221 DOI: 10.3389/fimmu.2021.584097
Abstract

High mobility group box 1 protein (HMGB1) is known to be a trigger of inflammation in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). However, it may play a different role in some way. Here we investigated the effect of HMGB1 on promoting sonic Hedgehog (shh) release from astrocytes as well as the possible signal pathway involved in it. Firstly, shh increased in astrocytes after administration of recombinant HMGB1 or decreased after HMGB1 was blocked when stimulated by homogenate of the onset stage of EAE. Moreover, the expression of HMGB1 receptors, Toll-like Receptor (TLR) 2 and receptor for advanced glycation end products (RAGE) increased after HMGB1 administration in primary astrocytes. However, the enhancing effect of HMGB1 on shh release from astrocytes was suppressed only after RAGE was knocked out or blocked. Mechanistically, HMGB1 functioned by activating RAGE-mediated JNK, p38, STAT3 phosphorylation. Moreover, HMGB1 could induce shh release in EAE. Additionally, intracerebroventricular injection of recombinant shh protein on the onset stage of EAE alleviated the progress of disease and decreased demylination, compared to the mice with normal saline treatment. Overall, HMGB1 promoted the release of shh from astrocytes through signal pathway JNK, p38 and STAT3 mediated by receptor RAGE, which may provide new insights of HMGB1 function in EAE.

Keywords

HMGB1; astrocytes; experimental autoimmune encephalomyelitis (EAE); receptor for advanced glycation end products (RAGE); sonic hedgehog (shh).

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