RNA-seq reveal RNA binding protein GNL3 as a key mediator in the development of psoriasis vulgaris by regulating the IL23/IL17 axis

Yao, Xiaomin; Zhu, Zhiwei; Manandhar, Upasana; Han, Liang; Yu, Tiexi; Wang, Yueying; Bian, Yawen; Zhang, Bo; Zhang, Xuanhong; Xie, Jun; Song, Jukun

doi:10.1016/j.lfs.2021.119902

Cited by 8 publications

(3 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed a significant downregulation of RNA modification, RNA splicing, and spliceosome pathways in cluster 0 KCs compared to cluster 1 KCs. These findings align with recent studies highlighting the involvement of these pathways in psoriasis ( 13 – 15 ). To investigate the transcriptional changes between KCs from normal and psoriasis skin tissues, we identified differentially expressed genes (DEGs).…”

Section: Resultssupporting

confidence: 92%

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Ma,

An,

Hao

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

BackgroundPsoriasis is an immune-mediated disorder influenced by environmental factors on a genetic basis. Despite advancements, challenges persist, including the diminishing efficacy of biologics and small-molecule targeted agents, alongside managing recurrence and psoriasis-related comorbidities. Unraveling the underlying pathogenesis and identifying valuable biomarkers remain pivotal for diagnosing and treating psoriasis.MethodsWe employed a series of bioinformatics (including single-cell sequencing data analysis and machine learning techniques) and statistical methods to integrate and analyze multi-level data. We observed the cellular changes in psoriatic skin tissues, screened the key genes Fatty acid binding protein 5 (FABP5) and The killer cell lectin-like receptor B1 (KLRB1), evaluated the efficacy of six widely prescribed drugs on psoriasis treatment in modulating the dendritic cell-associated pathway, and assessed their overall efficacy. Finally, RT-qPCR, immunohistochemistry, and immunofluorescence assays were used to validate.ResultsThe regulatory influence of dendritic cells (DCs) on T cells through the CD70/CD27 signaling pathway may emerge as a significant facet of the inflammatory response in psoriasis. Notably, FABP5 and KLRB1 exhibited up-regulation and co-localization in psoriatic skin tissues and M5-induced HaCaT cells, serving as potential biomarkers influencing psoriasis development.ConclusionOur study analyzed the impact of DC-T cell crosstalk in psoriasis, elucidated the characterization of two biomarkers, FABP5 and KLRB1, in psoriasis, and highlighted the promise and value of tofacitinib in psoriasis therapy targeting DCs.

show abstract

Section: Resultssupporting

confidence: 92%

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Ma,

An,

Hao

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…RNA-seq was performed as previously described 40 – 42 . Total RNA was extracted using TRIzol reagent according to the manufacturer’s protocol.…”

Section: Methodsmentioning

confidence: 99%

An MRTF-A–ZEB1–IRF9 axis contributes to fibroblast–myofibroblast transition and renal fibrosis

et al. 2023

View full text Add to dashboard Cite

Myofibroblasts, characterized by the expression of the matricellular protein periostin (Postn), mediate the profibrogenic response during tissue repair and remodeling. Previous studies have demonstrated that systemic deficiency in myocardin-related transcription factor A (MRTF-A) attenuates renal fibrosis in mice. In the present study, we investigated the myofibroblast-specific role of MRTF-A in renal fibrosis and the underlying mechanism. We report that myofibroblast-specific deletion of MRTF-A, achieved through crossbreeding Mrtfa-flox mice with Postn-CreERT2 mice, led to amelioration of renal fibrosis. RNA-seq identified zinc finger E-Box binding homeobox 1 (Zeb1) as a downstream target of MRTF-A in renal fibroblasts. MRTF-A interacts with TEA domain transcription factor 1 (TEAD1) to bind to the Zeb1 promoter and activate Zeb1 transcription. Zeb1 knockdown retarded the fibroblast–myofibroblast transition (FMyT) in vitro and dampened renal fibrosis in mice. Transcriptomic assays showed that Zeb1 might contribute to FMyT by repressing the transcription of interferon regulatory factor 9 (IRF9). IRF9 knockdown overcame the effect of Zeb1 depletion and promoted FMyT, whereas IRF9 overexpression antagonized TGF-β-induced FMyT. In conclusion, our data unveil a novel MRTF-A–Zeb1–IRF9 axis that can potentially contribute to fibroblast–myofibroblast transition and renal fibrosis. Screening for small-molecule compounds that target this axis may yield therapeutic options for the mollification of renal fibrosis.

show abstract

“…Th17 releases cytokines that stimulate IL10, IL20, and IL22 cytokines expression which results in keratinocyte hyperproliferation. This leads to more studies showing evidence that psoriasis is mainly driven by IL17/IL23/Th17 axis [131][132][133][134][135]. Hence, biologics targeting key cytokines, for instance, tumor necrosis factor alpha (TNF-α), interleukin-17 (IL-17), and interleukin-23 (IL-23), is a treatment option for psoriasis [136][137][138][139].…”

Section: Treatmentmentioning

confidence: 99%

Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis

et al. 2022

View full text Add to dashboard Cite

Evidence has shown that gut microbiome plays a role in modulating the development of diseases beyond the gastrointestinal tract, including skin disorders such as psoriasis. The gut–skin axis refers to the bidirectional relationship between the gut microbiome and skin health. This is regulated through several mechanisms such as inflammatory mediators and the immune system. Dysregulation of microbiota has been seen in numerous inflammatory skin conditions such as atopic dermatitis, rosacea, and psoriasis. Understanding how gut microbiome are involved in regulating skin health may lead to development of novel therapies for these skin disorders through microbiome modulation, in particularly psoriasis. In this review, we will compare the microbiota between psoriasis patients and healthy control, explain the concept of gut–skin axis and the effects of gut dysbiosis on skin physiology. We will also review the current evidence on modulating gut microbiome using probiotics in psoriasis.

show abstract

RNA-seq reveal RNA binding protein GNL3 as a key mediator in the development of psoriasis vulgaris by regulating the IL23/IL17 axis

Cited by 8 publications

References 42 publications

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

Single-cell sequencing analysis and multiple machine-learning models revealed the cellular crosstalk of dendritic cells and identified FABP5 and KLRB1 as novel biomarkers for psoriasis

An MRTF-A–ZEB1–IRF9 axis contributes to fibroblast–myofibroblast transition and renal fibrosis

Gut–Skin Axis: Unravelling the Connection between the Gut Microbiome and Psoriasis

Contact Info

Product

Resources

About