Prediction and Demonstration of Retinoic Acid Receptor Agonist Ch55 as an Antifibrotic Agent in the Dermis

Dolivo, David; Rodrigues, Adrian E.; Galiano, Robert D.; Mustoe, Thomas A.; Hong, Seok Jong

doi:10.1016/j.jid.2023.01.024

Cited by 2 publications

(1 citation statement)

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“…Since the presence and roles of myofibroblasts are somewhat conserved among fibrotic diseases of different tissues 5 , we hypothesized that LINC01013 might be overexpressed in human dermal myofibroblasts as well. Recently 6 , we generated RNA-seq data of human dermal fibroblasts cultured for 24 hours in the presence or absence of the pro-fibrotic cytokine TGF-β1 and the anti-fibrotic retinoic acid receptor agonist Ch55. We first re-analyzed this data ( Supplementary Methods ) in order to determine how expression of LINC01013 scaled with promotion and antagonism of dermal fibroblast activation.…”

Section: Letter Bodymentioning

confidence: 99%

Retrospective transcriptome analyses identifyLINC01013as an activation marker in human dermal fibroblasts

Dolivo¹,

Rodrigues²,

Galiano³

et al. 2023

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Study of fibroblast biology, including the process of fibroblast activation, is critical to our understanding of wound healing, tissue fibrosis, and cancer. However, the rapid adoption of next-generation sequencing technologies, particularly single-cell RNA-seq and spatial transcriptomics, has revealed that fibroblast heterogeneity of both healthy and pathological tissues is more complicated than we currently understand. Therefore, a better understanding of molecular players that are not only indicative of but also that contribute to fibroblast activation is critical to piecing together the complete picture and to informing therapeutic strategies to combat associated pathologies. Here we focus on a long-noncoding RNA, LINC01013, recently implicated in pathological activation of cardiac fibroblasts and valvular interstitial cell. We analyze several sets of publicly available human transcriptomic data with the aim of determining whether LINC01013 correlates with fibroblast activation state, and whether compounds that affect fibroblast activation also modulate expression of LINC01013. We find that, in numerous independent datasets of healthy and diseased human fibroblasts, LINC01013 expression is associated with fibroblast activation. We also describe that, even in datasets comprised of small sample sizes, statistically significant correlations exist between expression of LINC01013 and expression of fibroblast activation markers ACTA2 and CCN2. This finding, while preliminary, suggests that changes in LINC01013 expression may be an indicator of changes in fibroblast activation state, and that LINC01013 might functionally contribute to fibroblast activation, lending potential rationale for greater exploration of this lncRNA in the context of tissue fibrosis or tumor stroma.

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Section: Letter Bodymentioning

confidence: 99%