Effect of a monocyte chemoattractant protein-1 synthesis inhibitor on fibroblasts from patients with carpal tunnel syndrome

Yamanaka, Yoshiaki; Gingery, Anne; Oki, Gosuke; Yang, Tai-Hua; Zhao, Chunfeng; Amadio, Peter C.

doi:10.1016/j.jos.2020.03.010

Cited by 2 publications

(2 citation statements)

References 30 publications

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“…Moreover, a clinical trial indicated that CARLUMAB treatment did not provide benefit in patients with idiopathic pulmonary fibrosis ( 49 ). BINDARIT treatment may alleviate subsynovial connective tissues fibrosis in Carpal Tunnel Syndrome CTS and improved vascular dysfunction and lung inflammation in radiation-induced lung injury ( 50 , 51 ). These finding suggests that the therapeutic role of CARLUMAB and BINDARIT is also worth investigating in SSc.…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets

et al. 2023

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BackgroundSystemic sclerosis (SSc) is a rare autoimmune disease characterized by extensive skin fibrosis. There are no effective treatments due to the severity, multiorgan presentation, and variable outcomes of the disease. Here, integrated bioinformatics was employed to discover tissue-specific expressed hub genes associated with SSc, determine potential competing endogenous RNAs (ceRNA) regulatory networks, and identify potential targeted drugs.MethodsIn this study, four datasets of SSc were acquired. To identify the genes specific to tissues or organs, the BioGPS web database was used. For differentially expressed genes (DEGs), functional and enrichment analyses were carried out, and hub genes were screened and shown in a network of protein-protein interactions (PPI). The potential lncRNA–miRNA–mRNA ceRNA network was constructed using the online databases. The specifically expressed hub genes and ceRNA network were validated in the SSc mouse and in normal mice. We also used the receiver operating characteristic (ROC) curve to determine the diagnostic values of effective biomarkers in SSc. Finally, the Drug-Gene Interaction Database (DGIdb) identified specific medicines linked to hub genes.ResultsThe pooled datasets identified a total of 254 DEGs. The tissue/organ-specifically expressed genes involved in this analysis are commonly found in the hematologic/immune system and bone/muscle tissue. The enrichment analysis of DEGs revealed the significant terms such as regulation of actin cytoskeleton, immune-related processes, the VEGF signaling pathway, and metabolism. Cytoscape identified six gene cluster modules and 23 hub genes. And 4 hub genes were identified, including Serpine1, CCL2, IL6, and ISG15. Consistently, the expression of Serpine1, CCL2, IL6, and ISG15 was significantly higher in the SSc mouse model than in normal mice. Eventually, we found that MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1 may be promising RNA regulatory pathways in SSc. Besides, ten potential therapeutic drugs associated with the hub gene were identified.ConclusionsThis study revealed tissue-specific expressed genes, SERPINE1, CCL2, IL6, and ISG15, as effective biomarkers and provided new insight into the mechanisms of SSc. Potential RNA regulatory pathways, including MALAT1-miR-206-CCL2, let-7a-5p-IL6, and miR-196a-5p-SERPINE1, contribute to our knowledge of SSc. Furthermore, the analysis of drug-hub gene interactions predicted TIPLASININ, CARLUMAB and BINDARIT as candidate drugs for SSc.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets

et al. 2023

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“…Other conditions associated with debilitating pain in which fibroblasts contribute include chronic pain, in which fibroblasts are responsible for releasing proalgesic mediators and sustaining inflammatory responses ( 86 ), or carpal tunnel syndrome, a peripheral neuropathy characterised by fibrosis occurring in the subsynovial connective tissue in the carpal tunnel, with fibroblast hyperplasia, disorganised collagen deposition and increased expression of TGF-β1 pathway components ( 87 ). Therapies using typical antifibrotic strategies like targeting this profibrotic pathway have shown promising preliminary results in this syndrome ( 88 , 89 ).…”

Section: Fibroblasts In Health and Diseasementioning

confidence: 99%

Melanocortin therapies to resolve fibroblast-mediated diseases

et al. 2023

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Stromal cells have emerged as central drivers in multiple and diverse diseases, and consequently, as potential new cellular targets for the development of novel therapeutic strategies. In this review we revise the main roles of fibroblasts, not only as structural cells but also as players and regulators of immune responses. Important aspects like fibroblast heterogeneity, functional specialization and cellular plasticity are also discussed as well as the implications that these aspects may have in disease and in the design of novel therapeutics. An extensive revision of the actions of fibroblasts on different conditions uncovers the existence of numerous diseases in which this cell type plays a pathogenic role, either due to an exacerbation of their 'structural' side, or a dysregulation of their 'immune side'. In both cases, opportunities for the development of innovative therapeutic approaches exist. In this regard, here we revise the existing evidence pointing at the melanocortin pathway as a potential new strategy for the treatment and management of diseases mediated by aberrantly activated fibroblasts, including scleroderma or rheumatoid arthritis. This evidence derives from studies involving models of in vitro primary fibroblasts, in vivo models of disease as well as ongoing human clinical trials. Melanocortin drugs, which are pro-resolving mediators, have shown ability to reduce collagen deposition, activation of myofibroblasts, reduction of pro-inflammatory mediators and reduced scar formation. Here we also discuss existing challenges, both in approaching fibroblasts as therapeutic targets, and in the development of novel melanocortin drug candidates, that may help advance the field and deliver new medicines for the management of diseases with high medical needs.

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Effect of a monocyte chemoattractant protein-1 synthesis inhibitor on fibroblasts from patients with carpal tunnel syndrome

Cited by 2 publications

References 30 publications

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets

Bioinformatics-integrated screening of systemic sclerosis-specific expressed markers to identify therapeutic targets

Melanocortin therapies to resolve fibroblast-mediated diseases

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