PRMT6 deficiency or inhibition alleviates neuropathic pain by decreasing glycolysis and inflammation in microglia
Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved..
Microglia induced chronic inflammation is the critical pathology of Neuropathic pain (NP). Metabolic reprogramming of macrophage has been intensively reported in various chronic inflammation diseases. However, the metabolic reprogramming of microglia in chronic pain remains to be elusive. Here, we reported that immuno-metabolic markers (HIF-1α, PKM2, GLUT1 and lactate) were related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of the chronic construction injury (CCI) mice. PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis in the ipsilateral spinal cord dorsal horn. PRMT6 knockout or knockdown inhibited LPS-induced inflammation, proliferation and glycolysis in microglia cells. While PRMT6 overexpression exacerbated LPS-induced inflammation, proliferation and glycolysis in BV2 cells. Recent research revealed that PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. In sum, increased expression of PRMT6 exacerbates NP progress by increasing glycolysis and neuroinflammation through interacting with and stabilizing HIF-1α in a methyltransferase manner, which outlines novel pathological mechanism and drug target for NP.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:118 |
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| Enthalten in: |
Brain, behavior, and immunity - 118(2024) vom: 11. Apr., Seite 101-114 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Hua, Tong [VerfasserIn] |
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| Links: |
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| Themen: |
Immunometabolism |
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| Anmerkungen: |
Date Completed 10.04.2024 Date Revised 10.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbi.2024.02.027 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM368928950 |
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| 245 | 1 | 0 | |a PRMT6 deficiency or inhibition alleviates neuropathic pain by decreasing glycolysis and inflammation in microglia |
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| 520 | |a Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved. | ||
| 520 | |a Microglia induced chronic inflammation is the critical pathology of Neuropathic pain (NP). Metabolic reprogramming of macrophage has been intensively reported in various chronic inflammation diseases. However, the metabolic reprogramming of microglia in chronic pain remains to be elusive. Here, we reported that immuno-metabolic markers (HIF-1α, PKM2, GLUT1 and lactate) were related with increased expression of PRMT6 in the ipsilateral spinal cord dorsal horn of the chronic construction injury (CCI) mice. PRMT6 deficiency or prophylactic and therapeutic intrathecal administration of PRMT6 inhibitor (EPZ020411) ameliorated CCI-induced NP, inflammation and glycolysis in the ipsilateral spinal cord dorsal horn. PRMT6 knockout or knockdown inhibited LPS-induced inflammation, proliferation and glycolysis in microglia cells. While PRMT6 overexpression exacerbated LPS-induced inflammation, proliferation and glycolysis in BV2 cells. Recent research revealed that PRMT6 could interact with and methylate HIF-1α, which increased HIF-1α protein stability. In sum, increased expression of PRMT6 exacerbates NP progress by increasing glycolysis and neuroinflammation through interacting with and stabilizing HIF-1α in a methyltransferase manner, which outlines novel pathological mechanism and drug target for NP | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Immunometabolism | |
| 650 | 4 | |a Microglia | |
| 650 | 4 | |a Neuroinflammation | |
| 650 | 4 | |a Neuropathic pain | |
| 650 | 4 | |a PRMT6 | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 700 | 1 | |a Kong, Erliang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Hailing |e verfasserin |4 aut | |
| 700 | 1 | |a Lu, Jinfang |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Kesheng |e verfasserin |4 aut | |
| 700 | 1 | |a Ding, Ruifeng |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Haowei |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Jian |e verfasserin |4 aut | |
| 700 | 1 | |a Han, Chaofeng |e verfasserin |4 aut | |
| 700 | 1 | |a Yuan, Hongbin |e verfasserin |4 aut | |
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