&lt;p&gt;Immunohistochemical study of janus kinase 1/signal transducer and activator of transcription 3 in psoriasis vulgaris&lt;/p&gt;

Farag, Azza Gaber Antar; Samaka, Rehab M; El-Shafey, Eman N; Shehata, Wafaa Ahmed; Sherbiny, Eman Gamal El; Hammam, M. A.

doi:10.2147/ccid.s202835

Cited by 9 publications

(11 citation statements)

References 28 publications

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“…[ 15 ] STAT3 is also involved in cellular proliferation and apoptosis, and it is significantly overexpressed in psoriatic skin lesions. [ 8 16 ] In our study, whether at gene level or at protein level, whether in psoriatic skin lesions or in non-lesion skin, the results show STAT3 is upregulated while in miR-31 overexpression.…”

Section: Discussionmentioning

confidence: 59%

“…Signal transducer and activator of transcription 3 (STAT3), as a transcription factor, can regulate cytokines and growth factor,[ 6 ] and can cause cell proliferation. [ 7 8 ] P53, as tumor suppressor protein, can suppress tumor growth by controlling cell cycle and DNA replication. [ 9 ] Currently, the study of both focus largely on tumor.…”

Section: Introductionmentioning

confidence: 99%

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MicroRNA-31 Overexpression may Aggravate the Formation of Psoriasis-like Lesions by STAT3/p53 Pathway

Wang

Zhao

et al. 2021

Indian Journal of Dermatology

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Background: Psoriasis is a chronic inflammatory skin disease with an unknown pathogenesis. Recently, miR-31 have been shown to play an important role in psoriasis. Moreover, STAT3/p53 pathway has been used in tumor studies, but rarely in psoriasis studies. Aims: The present study aimed to investigate the role of STAT3/p53 pathway in psoriasis-like lesions in a mouse model of miR-31 overexpression. Methods: All mice (n = 44) were divided into four groups: normal mice treated with Vaseline® (NV; n = 10), normal mice treated with imiquimod (NI; n = 12), miR-31-overexpressing mice treated with Vaseline® (MV; n = 10), and miR-31-overexpressing mice treated with imiquimod (MI; n = 12). Then, we assayed the expression of STAT3 and p53. Results: Our results showed that at the protein level (P < 0.01) and gene level (4.45 times), the expression of STAT3 in the MV group was higher than that in the NV group, and at the protein level (P < 0.01) and gene level (11.43 times), the expression of STAT3 in the MI group was higher than that in the NI group. At the protein level, the expression of p53 in MV group was higher than that in the NV group (P < 0.05), and the expression of p53 in MI group was higher than that in the NI group (P < 0.01). Conclusions: Our findings indicate that overexpression of miR-31 causes upregulation of STAT3, which further brings about upregulation of p53, and eventually leads to serious psoriasis skin lesion.

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Section: Discussionmentioning

confidence: 59%

Section: Introductionmentioning

confidence: 99%

MicroRNA-31 Overexpression may Aggravate the Formation of Psoriasis-like Lesions by STAT3/p53 Pathway

Wang

Zhao

et al. 2021

Indian Journal of Dermatology

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“…The histoscore (H-score) was applied to KFs and NFs in the dermis, where both the percentage and the intensity of the positive staining were considered. H-score = 1 × the percentage of mildly stained fibroblasts +2 × the percentage of moderately stained fibroblasts +3 × the percentage of strongly stained fibroblasts [ 31 ].…”

Section: Methodsmentioning

confidence: 99%

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

Wang

Zhong

et al. 2022

Burns &Amp; Trauma

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Background A keloid is a disease of excessive fibrosis that is characterized by the aberrant proliferation of fibroblasts. However, the molecular mechanisms of fibroblasts during the development of keloids remain unclear. This study aims to identify new molecular targets that promote the proliferation and migration of keloid fibroblasts, providing new ideas for the prevention and treatment of keloids. Methods We utilized bioinformatics tools to analyze data from keloid fibroblasts (KFs) available in the Gene Expression Omnibus (GEO) database to identify the key genes involved in keloid development. Homeobox C6 (HOXC6) emerged as a hub gene in KFs from the GEO database was verified in keloid tissue samples and KFs using reverse transcription-quantitative polymerase chain reaction, western blot (WB) and immunohistochemistry. Subsequently, the effects of downregulated HOXC6 expression on the cellular behaviors of KFs were examined by performing Cell Counting Kit-8, flow cytometry, transwell migration and WB assays. Meanwhile, we performed transcriptome sequencing and gene set enrichment analysis (GSEA) to further explore HOXC6-related mechanisms and validated the signaling pathways by performing a series of experiments. Results HOXC6 was the top-ranking hub gene of KFs in microarray datasets from GEO and was upregulated in keloid tissue samples and KFs. Downregulation of HOXC6 inhibited proliferation, migration and extracellular matrix (ECM) accumulation and promoted KF apoptosis. GSEA predicted that the hypoxia signaling pathway was associated with HOXC6 in KFs. Transcriptome sequencing suggested that the extracellular regulated protein kinase (ERK) pathway was one of the downstream pathways of HOXC6 in KFs. Our experiments confirmed that hypoxia-inducible factor-1α (HIF-1α) upregulates HOXC6, contributing to KFs proliferation, migration, apoptosis inhibition and collagen accumulation through the ERK signaling pathway. Conclusions Our findings first revealed that HOXC6 acts as an oncogenic driver in the molecular mechanisms of fibroblasts in keloids. The HIF-1α/HOXC6/ERK axis promotes proliferation, migration and ECM production by KFs, contributing to the progression of keloids. Taken together, HOXC6 may serve as a promising novel therapeutic target and new focus for research designed to understand the pathogenesis of keloids.

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“…JAK1 gain-of-function was reported in psoriasis. 147 JAK1 gain-of-function mutations resulted in complex autoinflammatory syndrome, 148 in hypereosinophilic syndrome, 149 in myeloproliferative neoplasm. 150 …”

Section: Jak1 Gain-of-function Mutations Are Frequent In “Low Treg” Dmentioning

confidence: 99%

The Binary Classification of Protein Kinases

Elkoshi¹

2021

JIR

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In an earlier publication a binary model for chronic diseases classification has been proposed. According to the model, chronic diseases were classified as “high Treg” or “low Treg” diseases, depending on whether the immune response is anti- or pro-inflammatory and assuming that regulatory T cells are major determinants of the response. It turned out that most cancers are “high Treg” diseases, while autoimmune diseases are “low Treg”. This paper proposes a molecular cause for this binary response. The mechanism proposed depends on the effect of protein kinases on the immune system. Thus, protein kinases are classified as anti- or pro-inflammatory kinases depending on whether they drive “high Treg” or “low Treg” diseases. Observations reported in the earlier publication can be described in terms of anti-inflammatory kinase (AIK) or pro-inflammatory kinase (PIK) activity. Analysis of literature data reveals that the two classes of kinases display distinctive properties relating to their interactions with pathogens and environmental factors. Pathogens that promote Treg activity (“high Treg” pathogens) activate AIKs, while pathogens that suppress Treg activity (“low Treg” pathogens) activate PIKs. Diseases driven by AIKs are associated with “high Treg” pathogens while those diseases driven by PIKs are associated with “low Treg” pathogens. By promoting the activity of AIKs, alcohol consumption increases the risk of “high Treg” cancers but decreases the risk of some “low Treg” autoimmune diseases. JAK1 gain-of-function mutations are observed at high frequencies in autoimmune diseases while JAK1 loss-of-function mutations are observed at high frequencies in cancers with high tumor-infiltrating Tregs. It should also be noted that the corresponding two classes of protein kinase inhibitors are mutually exclusive in terms of their approved therapeutic indications. There is no protein kinase inhibitor that is approved for the treatment of both autoimmune diseases and “high Treg” cancers. Although there are exceptions to the conclusions presented above, these conclusions are supported by the great bulk of published data. It therefore seems that the binary division of protein kinases is a useful tool for elucidating (at the molecular level) many distinctive properties of cancers and autoimmune diseases.

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<p>Immunohistochemical study of janus kinase 1/signal transducer and activator of transcription 3 in psoriasis vulgaris</p>

Cited by 9 publications

References 28 publications

MicroRNA-31 Overexpression may Aggravate the Formation of Psoriasis-like Lesions by STAT3/p53 Pathway

MicroRNA-31 Overexpression may Aggravate the Formation of Psoriasis-like Lesions by STAT3/p53 Pathway

Multitranscriptome analyses of keloid fibroblasts reveal the role of the HIF-1α/HOXC6/ERK axis in keloid development

The Binary Classification of Protein Kinases

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