Increased expression of bone/cartilage‐associated genes and core transcription factors in keloids by <scp>RNA</scp> sequencing

Lin, Pingping; Zhang, Guohong; Peng, Rui; Zhao, Mingming; Li, Hang

doi:10.1111/exd.14630

Cited by 6 publications

(7 citation statements)

References 40 publications

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“…Previous bioinformatics analysis has demonstrated that COL5A2, COL10A1, and COL11A1 may be used as a diagnostic or prognostic biomarker for tumors such as gastric cancer ( Niu et al, 2022 ), breast carcinoma ( Giussani et al, 2018 ), and non-small-cell lung cancer ( Andriani et al, 2018 ). According to the findings of RNA sequencing, COL5A2, COL10A1, and COL11A1 have been reported to be upregulated in keloid ( Bi et al, 2021 ; Lin P. et al, 2022 ), as in our study. A whole-exome sequencing study revealed that COL5A2 is relevant to the fibrotic features of diffuse cutaneous SSc ( Mak et al, 2016 ).…”

Section: Discussionsupporting

confidence: 83%

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases

Jin

Chen

et al. 2023

Front. Genet.

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Background: Fibrotic skin diseases are characterized by excessive accumulation of the extracellular matrix (ECM) and activation of fibroblasts, leading to a global healthcare burden. However, effective treatments of fibrotic skin diseases remain limited, and their pathological mechanisms require further investigation. This study aims to investigate the common biomarkers and therapeutic targets in two major fibrotic skin diseases, namely, keloid and systemic sclerosis (SSc), by bioinformatics analysis.Methods: The keloid (GSE92566) and SSc (GSE95065) datasets were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified, followed by functional enrichment analysis using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We then constructed a protein–protein interaction (PPI) network for the identification of hub genes. We explored the possibility of further functional enrichment analysis of hub genes on the Metascape, GeneMANIA, and TissueNexus platforms. Transcription factor (TF)–hub gene and miRNA–hub gene networks were established using NetworkAnalyst. We fixed GSE90051 and GSE76855 as the external validation datasets. Student’s t-test and receiver operating characteristic (ROC) curve were used for candidate hub gene validation. Hub gene expression was assessed in vitro by quantitative real-time PCR.Results: A total of 157 overlapping DEGs (ODEGs) were retrieved from the GSE92566 and GSE95065 datasets, and five hub genes (COL11A1, COL5A2, ASPN, COL10A1, and COMP) were identified and validated. Functional studies revealed that hub genes were predominantly enriched in bone/cartilage-related and collagen-related processes. FOXC1 and miR-335-5p were predicted to be master regulators at both transcriptional and post‐transcriptional levels.Conclusion: COL11A1, COL5A2, ASPN, COL10A1, and COMP may help understand the pathological mechanism of the major fibrotic skin diseases; moreover, FOXC1 and miR-355-5p could build a regulatory network in keloid and SSc.

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Section: Discussionsupporting

confidence: 83%

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases

Jin

Chen

et al. 2023

Front. Genet.

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“…Report of elevation of chondrocyte/osteoblast marker genes, including SOX9 and CBFA1 , in keloids has been previously described ( Naitoh et al., 2005 ). Upregulation of genes involved in bone and cartilage formation has also been published ( Inui et al., 2011 ) in African American subjects ( BMP1 , RUNX2 , and CDH11 ) ( Fuentes-Duculan et al., 2017 ) and more recently in another cohort ( Lin et al., 2022 ). It must be noted that Lin et al.…”

Section: Discussionmentioning

confidence: 92%

“…Upregulation of genes involved in bone and cartilage formation has also been published ( Inui et al., 2011 ) in African American subjects ( BMP1 , RUNX2 , and CDH11 ) ( Fuentes-Duculan et al., 2017 ) and more recently in another cohort ( Lin et al., 2022 ). It must be noted that Lin et al. (2022) specifically reported no change in COL2A1 levels between control and keloid dermal tissues, with extremely low expression in all samples.…”

Section: Discussionmentioning

confidence: 92%

Defining a Unique Gene Expression Profile in Mature and Developing Keloids

et al. 2023

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“…Lin et al sequenced 6 keloid dermis and compared them with control dermis, showing that AEBP1 was among the candidate core regulators that promote the bone/cartilage-like characteristics in keloids. In addition, RNA-Seq of full-skin keloids and IHC experiments consolidated the role of this molecule ( 51 ). AEBP1 also enhances adipose tissue stromal progenitor differentiation into myofibroblasts and is upregulated in fibrotic white adipose tissue ( 50 ).…”

Section: Discussionmentioning

confidence: 99%

Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator

Corano Scheri,

Lavine,

Tedeschi

et al. 2023

JCI Insight

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The management of preretinal fibrovascular membranes, a devastating complication of advanced diabetic retinopathy (DR), remains challenging. We characterized the molecular profile of cell populations in these fibrovascular membranes to identify potentially new therapeutic targets. Preretinal fibrovascular membranes were surgically removed from patients and submitted for single-cell RNA-Seq (scRNA-Seq). Differential gene expression was implemented to define the transcriptomics profile of these cells and revealed the presence of endothelial, inflammatory, and stromal cells. Endothelial cell reclustering identified subclusters characterized by noncanonical transcriptomics profile and active angiogenesis. Deeper investigation of the inflammatory cells showed a subcluster of macrophages expressing proangiogenic cytokines, presumably contributing to angiogenesis. The stromal cell cluster included a pericyte-myofibroblast transdifferentiating subcluster, indicating the involvement of pericytes in fibrogenesis. Differentially expressed gene analysis showed that Adipocyte Enhancer-binding Protein 1, AEBP1 , was significantly upregulated in myofibroblast clusters, suggesting that this molecule may have a role in transformation. Cell culture experiments with human retinal pericytes (HRP) in high-glucose condition confirmed the molecular transformation of pericytes toward myofibroblastic lineage. AEBP1 siRNA transfection in HRP reduced the expression of profibrotic markers in high glucose. In conclusion, AEBP1 signaling modulates pericyte-myofibroblast transformation, suggesting that targeting AEBP1 could prevent scar tissue formation in advanced DR.

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Increased expression of bone/cartilage‐associated genes and core transcription factors in keloids by RNA sequencing

Cited by 6 publications

References 40 publications

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases

Identification and characterization of bone/cartilage-associated signatures in common fibrotic skin diseases

Defining a Unique Gene Expression Profile in Mature and Developing Keloids

Single-cell transcriptomics analysis of proliferative diabetic retinopathy fibrovascular membranes reveals AEBP1 as fibrogenesis modulator

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