The role of the extracellular matrix in chronic pain following injury

Tajerian, Maral; Clark, J. David

doi:10.1097/01.j.pain.0000460323.80020.9d

Cited by 25 publications

(25 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The ECM has been implicated in tissue homeostasis, as well as pathological processes triggered by nerve injury in the SC (Bartus et al, 2014 ; Tajerian and Clark, 2015 ). In chronic pain conditions, there is accumulating evidence for the role of ECM changes in hypersensitivity and long lasting maladaptation, particularly by affecting synaptic plasticity in the CNS (Tajerian and Clark, 2015 ). Yet, details about the role of its protein constituents for PNS (patho-) physiology remain to be investigated.…”

Section: Discussionmentioning

confidence: 99%

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord

Barry

Sondermann

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

To obtain a thorough understanding of chronic pain, large-scale molecular mapping of the pain axis at the protein level is necessary, but has not yet been achieved. We applied quantitative proteome profiling to build a comprehensive protein compendium of three regions of the pain neuraxis in mice: the sciatic nerve (SN), the dorsal root ganglia (DRG), and the spinal cord (SC). Furthermore, extensive bioinformatics analysis enabled us to reveal unique protein subsets which are specifically enriched in the peripheral nervous system (PNS) and SC. The immense value of these datasets for the scientific community is highlighted by validation experiments, where we monitored protein network dynamics during neuropathic pain. Here, we resolved profound region-specific differences and distinct changes of PNS-enriched proteins under pathological conditions. Overall, we provide a unique and validated systems biology proteome resource (summarized in our online database painproteome.em.mpg.de), which facilitates mechanistic insights into somatosensory biology and chronic pain—a prerequisite for the identification of novel therapeutic targets.

show abstract

Section: Discussionmentioning

confidence: 99%

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord

Barry

Sondermann

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The disarray of different ECM structural proteins and the altered expression of genes involved in ECM remodeling should play a role not only in the generation of inflammation, but also in the neuronal plasticity and hyperexcitability of nociceptive neurons and in the chronification of pain observed in JHS/EDS-HT patients [ 38 ]. It is well established that ECM molecules or fragments released by matrix metallopeptidases activating in response to injury and integrin-mediated responses, could modulate inflammatory pathways and hyperalgesic signaling [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

Chiarelli¹,

Carini²,

Zoppi³

et al. 2016

PLoS ONE

View full text Add to dashboard Cite

Joint hypermobility syndrome/Ehlers–Danlos syndrome hypermobility type (JHS/EDS-HT), is likely the most common systemic heritable connective tissue disorder, and is mostly recognized by generalized joint hypermobility, joint instability complications, minor skin changes and a wide range of satellite features. JHS/EDS-HT is considered an autosomal dominant trait but is still without a defined molecular basis. The absence of (a) causative gene(s) for JHS/EDS-HT is likely attributable to marked genetic heterogeneity and/or interaction of multiple loci. In order to help in deciphering such a complex molecular background, we carried out a comprehensive immunofluorescence analysis and gene expression profiling in cultured skin fibroblasts from five women affected with JHS/EDS-HT. Protein study revealed disarray of several matrix structural components such as fibrillins, tenascins, elastin, collagens, fibronectin, and their integrin receptors. Transcriptome analysis indicated perturbation of different signaling cascades that are required for homeostatic regulation either during development or in adult tissues as well as altered expression of several genes involved in maintenance of extracellular matrix architecture and homeostasis (e.g., SPON2, TGM2, MMP16, GPC4, SULF1), cell-cell adhesion (e.g., CDH2, CHD10, PCDH9, CLDN11, FLG, DSP), immune/inflammatory/pain responses (e.g., CFD, AQP9, COLEC12, KCNQ5, PRLR), and essential for redox balance (e.g., ADH1C, AKR1C2, AKR1C3, MAOB, GSTM5). Our findings provide a picture of the gene expression profile and dysregulated pathways in JHS/EDS-HT skin fibroblasts that correlate well with the systemic phenotype of the patients.

show abstract

“…Indeed, it is recognized that intracellular molecules released from damaged tissues, as well as fragments of the ECM released downstream cell injury, can act as damage-associated molecular patterns (DAMPs). These molecules serve as danger signals that can elicit an immune response following tissue injury or in response to the changes in tissue composition and organization [ 156 , 157 , 158 , 159 , 160 ]. In this light, it is reasonable to assume that in hEDS/HSD cells these molecules may act as DAMPs and could be recognized by the αvβ3 integrin or other specialized receptors, which turn on pathways that transduce for the synthesis of a plethora of inflammation molecules.…”

Section: The αVβ3 Integrin Signaling Sustains the Hypermobile Eds mentioning

confidence: 99%

Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

Zoppi

Chiarelli

Ritelli

et al. 2018

IJMS

View full text Add to dashboard Cite

The αvβ3 integrin, an endothelial cells’ receptor-binding fibronectin (FN) in the extracellular matrix (ECM) of blood vessels, regulates ECM remodeling during migration, invasion, angiogenesis, wound healing and inflammation, and is also involved in the epithelial mesenchymal transition. In vitro-grown human control fibroblasts organize a fibrillar network of FN, which is preferentially bound on the entire cell surface to its canonical α5β1 integrin receptor, whereas the αvβ3 integrin is present only in rare patches in focal contacts. We report on the preferential recruitment of the αvβ3 integrin, due to the lack of FN–ECM and its canonical integrin receptor, in dermal fibroblasts from Ehlers–Danlos syndromes (EDS) and arterial tortuosity syndrome (ATS), which are rare multisystem connective tissue disorders. We review our previous findings that unraveled different biological mechanisms elicited by the αvβ3 integrin in fibroblasts derived from patients affected with classical (cEDS), vascular (vEDS), hypermobile EDS (hEDS), hypermobility spectrum disorders (HSD), and ATS. In cEDS and vEDS, respectively, due to defective type V and type III collagens, αvβ3 rescues patients’ fibroblasts from anoikis through a paxillin-p60Src-mediated cross-talk with the EGF receptor. In hEDS and HSD, without a defined molecular basis, the αvβ3 integrin transduces to the ILK-Snail1-axis inducing a fibroblast-to-myofibroblast-transition. In ATS cells, the deficiency of the dehydroascorbic acid transporter GLUT10 leads to redox imbalance, ECM disarray together with the activation of a non-canonical αvβ3 integrin-TGFBRII signaling, involving p125FAK/p60Src/p38MAPK. The characterization of these different biological functions triggered by αvβ3 provides insights into the multifaced nature of this integrin, at least in cultured dermal fibroblasts, offering future perspectives for research in this field.

show abstract

The role of the extracellular matrix in chronic pain following injury

Cited by 25 publications

References 58 publications

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord

Region-Resolved Quantitative Proteome Profiling Reveals Molecular Dynamics Associated With Chronic Pain in the PNS and Spinal Cord

Transcriptome-Wide Expression Profiling in Skin Fibroblasts of Patients with Joint Hypermobility Syndrome/Ehlers-Danlos Syndrome Hypermobility Type

Multifaced Roles of the αvβ3 Integrin in Ehlers–Danlos and Arterial Tortuosity Syndromes’ Dermal Fibroblasts

Contact Info

Product

Resources

About