SRGN is a Potential Preclinical Diagnostic Biomarker and Therapeutic Target for Intervertebral Disc Degeneration

Chen, Fan; Lei, Linchuan; Chen, Shunlun; Zhao, Zhuoyang; Huang, Yuming; Jiang, Guotai; Guo, Xingyu; Li, Zemin; Zheng, Zhaomin; Wang, Jianru

doi:10.2139/ssrn.4165639

Cited by 1 publication

(1 citation statement)

References 28 publications

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“…Together these findings suggest an increase in the number of type M2 macrophages in DRGs of Pv-cKO-FXN, which may thus promote inflammation resolution rather than a pro-inflammatory response 42,51 . In agreement we observed upregulation of genes known for their implication in extracellular matrix remodeling (Adamts1, Srgn, Igfbp5 ; Figure 5) and endothelial cell permeability (Emp1), which all may elicit immune cell extravasation and infiltration into DRGs 33,[52][53][54][55] . The expression of Adamts1 and Igfbp5 in DRG endothelial cells and/or pericytes as well as the expression of Srgn in endothelial cells and macrophage 24 further support the idea of an increased influx of macrophages.…”

Section: Fxn Loss In Proprioceptors Caused Changes In Inflammatory Ge...supporting

confidence: 83%

Frataxin deficiency in proprioceptive neurons is causal to inflammatory and glial responses in dorsal root ganglia

Meriau,

Weill,

Puccio

et al. 2024

Preprint

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Friedreich ataxia (FA), the most common recessive hereditary ataxia, is an early-onset neurodegenerative disease characterized by pathological changes occurring first in the peripheral dorsal root ganglia (DRG), with loss of the large sensory proprioceptive neurons, leading to ganglionopathy and proprioceptive deficits. FA is caused by a mutation in frataxin gene (Fxn), leading to reduced expression of frataxin protein (FXN), an essential ubiquitous mitochondrial protein. Most research has focused on the pathophysiological involvement of proprioceptors. However, in recent years, neuroinflammation is increasingly recognized as an integral and critical contributor in FA pathogenesis. Furthermore, it has also recently been shown a primary reactivity of satellite glial cells (SGCs; glia tightly enwrapping proprioceptor cell bodies), suggesting a role of inflammation and SGC responses in the destruction of proprioceptors in FA patients' DRGs. It remains unclear to what extent the increase in DRG macrophage response and/or SGC reactivity may contribute to FA phenotype. Therefore, it is important to fully study and understand the mechanism of proprioceptor-macrophages-SGC interactions and their regulations. Exploring relationship between these three cell types has profound implications for breaking through the limitation of treatment of FA. Here we asked whether FXN deficiency selectively in DRG proprioceptive neurons is sufficient to cause inflammatory and glial responses found in patients' DRG. We used RNA profiling, bioinformatics signaling network and pathway analysis, combined with immunohistochemistry and behavioral experiments to reveal some genes, signaling pathways in macrophages and SGCs that may represent potential biomarkers of the disease. Our study revealed that proprioceptor FXN deficiency causes major changes in inflammatory macrophage and SGC gene transcription as well as macrophage and SGC number, highlighting molecular and cellular pathways that were sequentially altered, thus representing temporal signatures of FA ganglionopathy progression.

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Section: Fxn Loss In Proprioceptors Caused Changes In Inflammatory Ge...supporting

confidence: 83%

Frataxin deficiency in proprioceptive neurons is causal to inflammatory and glial responses in dorsal root ganglia

Meriau,

Weill,

Puccio

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

SRGN is a Potential Preclinical Diagnostic Biomarker and Therapeutic Target for Intervertebral Disc Degeneration

Cited by 1 publication

References 28 publications

Frataxin deficiency in proprioceptive neurons is causal to inflammatory and glial responses in dorsal root ganglia

Frataxin deficiency in proprioceptive neurons is causal to inflammatory and glial responses in dorsal root ganglia

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