The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis
Is Associated with a Pro-Regenerative State in Cervical Primary
Sensory Neurons Conditioned by a Sciatic Nerve Lesion

J 2025

The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion

DUBOVÝ, Petr; Ivana HRADILOVÁ SVÍŽENSKÁ; Václav BRÁZDA; Anna JAMBRICHOVÁ; Viktorie SVOBODOVÁ et. al.

Basic information

Original name

The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion

Authors

DUBOVÝ, Petr (203 Czech Republic, belonging to the institution); Ivana HRADILOVÁ SVÍŽENSKÁ (203 Czech Republic, belonging to the institution); Václav BRÁZDA (203 Czech Republic, belonging to the institution); Anna JAMBRICHOVÁ (703 Slovakia, belonging to the institution); Viktorie SVOBODOVÁ (203 Czech Republic, belonging to the institution) and Marek JOUKAL (203 Czech Republic, belonging to the institution)

Edition

International Journal of Molecular Sciences, BASEL, MDPI, 2025, 1661-6596

Other information

Language

English

Type of outcome

Article in a journal

Field of Study

30103 Neurosciences

Country of publisher

Switzerland

Confidentiality degree

is not subject to a state or trade secret

References:

URL

Impact factor

Impact factor: 4.900 in 2024

Organization unit

Faculty of Medicine

DOI

https://doi.org/10.3390/ijms26010193

UT WoS

001393708700001

EID Scopus

2-s2.0-85214493883

Keywords in English

sciatic nerve; transection; pre-conditioning; axon regeneration; AMD3100; IL-6; STAT3

Abstract

In the original language

CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of na & iuml;ve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons. The role of CXCR4 signaling in the axon-promoting state of DRG neurons was confirmed through in vitro cultivation of primary sensory neurons in a medium supplemented with CXCL12, with or without AMD3100. The potential involvement of conditioned cervical DRG neurons in the induction of neuropathic pain is discussed.

Links

GA16-08508S, research and development project

Name: Zvýšení endogenního regeneračního programu a jeho aktivace zprostředkovaná cytokiny/chemokiny v neuronech ganglií bez spojení s poškozeným nervem (Acronym: ERP)

Investor: Czech Science Foundation

MUNI/A/1563/2023, interní kód MU

Name: Funkční morfologie: od molekulární biologie ke klinické anatomii 3

Investor: Masaryk University

Cite

DUBOVÝ, Petr; Ivana HRADILOVÁ SVÍŽENSKÁ; Václav BRÁZDA; Anna JAMBRICHOVÁ; Viktorie SVOBODOVÁ and Marek JOUKAL. The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion. International Journal of Molecular Sciences. BASEL: MDPI, 2025, vol. 26, No 1, p. 1-22. ISSN 1661-6596. Available from: https://doi.org/10.3390/ijms26010193.

@article{2471999,
   author = {Dubový, Petr and Hradilová Svíženská, Ivana and Brázda, Václav and Jambrichová, Anna and Svobodová, Viktorie and Joukal, Marek},
   article_location = {BASEL},
   article_number = {1},
   doi = {https://doi.org/10.3390/ijms26010193},
   keywords = {sciatic nerve; transection; pre-conditioning; axon regeneration; AMD3100; IL-6; STAT3},
   language = {eng},
   issn = {1661-6596},
   journal = {International Journal of Molecular Sciences},
   title = {The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion},
   url = {https://www.mdpi.com/1422-0067/26/1/193},
   volume = {26},
   year = {2025}
}

TY  - JOUR
ID  - 2471999
AU  - Dubový, Petr - Hradilová Svíženská, Ivana - Brázda, Václav - Jambrichová, Anna - Svobodová, Viktorie - Joukal, Marek
PY  - 2025
TI  - The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion
JF  - International Journal of Molecular Sciences
VL  - 26
IS  - 1
SP  - 1-22
EP  - 1-22
PB  - MDPI
SN  - 16616596
KW  - sciatic nerve
KW  - transection
KW  - pre-conditioning
KW  - axon regeneration
KW  - AMD3100
KW  - IL-6
KW  - STAT3
UR  - https://www.mdpi.com/1422-0067/26/1/193
N2  - CXCL12 and CXCR4 proteins and mRNAs were monitored in the dorsal root ganglia (DRGs) of lumbar (L4-L5) and cervical (C7-C8) spinal segments of na & iuml;ve rats, rats subjected to sham operation, and those undergoing unilateral complete sciatic nerve transection (CSNT) on post-operation day 7 (POD7). Immunohistochemical, Western blot, and RT-PCR analyses revealed bilaterally increased levels of CXCR4 protein and mRNA in both lumbar and cervical DRG neurons after CSNT. Similarly, CXCL12 protein levels increased, and CXCL12 mRNA was upregulated primarily in lumbar DRGs ipsilateral to the nerve lesion. Intrathecal application of the CXCR4 inhibitor AMD3100 following CSNT reduced CXCL12 and CXCR4 protein levels in cervical DRG neurons, as well as the length of afferent axons regenerated distal to the ulnar nerve crush. Furthermore, treatment with the CXCR4 inhibitor decreased levels of activated Signal Transducer and Activator of Transcription 3 (STAT3), a critical transforming factor in the neuronal regeneration program. Administration of IL-6 increased CXCR4 levels, whereas the JAK2-dependent STAT3 phosphorylation inhibitor (AG490) conversely decreased CXCR4 levels. This indicates a link between the CXCL12/CXCR4 signaling axis and IL-6-induced activation of STAT3 in the sciatic nerve injury-induced pro-regenerative state of cervical DRG neurons. The role of CXCR4 signaling in the axon-promoting state of DRG neurons was confirmed through in vitro cultivation of primary sensory neurons in a medium supplemented with CXCL12, with or without AMD3100. The potential involvement of conditioned cervical DRG neurons in the induction of neuropathic pain is discussed.
ER  -

DUBOVÝ, Petr; Ivana HRADILOVÁ SVÍŽENSKÁ; Václav BRÁZDA; Anna JAMBRICHOVÁ; Viktorie SVOBODOVÁ and Marek JOUKAL. The Intrinsic Neuronal Activation of the CXCR4 Signaling Axis Is Associated with a Pro-Regenerative State in Cervical Primary Sensory Neurons Conditioned by a Sciatic Nerve Lesion. \textit{International Journal of Molecular Sciences}. BASEL: MDPI, 2025, vol.~26, No~1, p.~1-22. ISSN~1661-6596. Available from: https://doi.org/10.3390/ijms26010193.

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