MicroRNA‐215‐5p inhibits the proliferation of keratinocytes and alleviates psoriasis‐like inflammation by negatively regulating DYRK1A and its downstream signalling pathways

Liu, Aimin; Zhang, Buxin; Zhao, Wei; Tu, Yuanhui; Wang, Qingxing; Li, Jing

doi:10.1111/exd.14188

Cited by 11 publications

(7 citation statements)

References 38 publications

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“…In our analysis, multiple mTOR signaling complex molecules are direct targets of miR125b and miR-148 in light of the key role of the axis in abnormal keratinocyte proliferation and differentiation and modulating T cell metabolism, cell proliferation, activation, and differentiation ( 50 , 51 , 72 , 74 , 76 ). EGFR signaling, modulable via miR-215-targeted dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRKA1), is another molecular module that leads to keratinocyte hyperproliferation ( 52 ). The KC innervation pathway comprises Semaphorin 3A (Sema 3A) as a direct target of miR-142-3p, with implications for keratinocyte proliferation, apoptosis, and the production of inflammatory mediators ( 53 ).…”

Section: Resultsmentioning

confidence: 99%

A panel of blood-based circulatory miRNAs with diagnostic potential in patients with psoriasis

Madaan,

Sharma,

Tyagi

et al. 2023

Front. Med.

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Psoriasis is a chronic inflammatory skin disease with keratinocyte hyperproliferation and T cells as key mediators of lesional and systemic inflammatory changes. To date, no suitable differential biomarkers are available for the disease diagnosis. More recently, microRNAs have been identified as critical regulators of lesional and systemic immune changes in psoriasis with diagnostic potential. We have performed expression profiling of T cell-specific miRNAs in 38 plasma samples from psoriasis vulgaris patients and an equal number of age- and gender-matched healthy subjects. Our findings have identified a panel of five blood-based circulatory miRNAs with a significant change in their expression levels, comprising miR-215, miR-148a, miR-125b-5p, miR-223, and miR-142-3p, which can differentiate psoriasis vulgaris patients from healthy individuals. The receiver operating characteristic (ROC) curves for all five miRNAs individually and in combination exhibited a significant disease discriminatory area under the curve with an AUC of 0.762 and a p < 0.0001 for all the miRNAs together. Statistically, all five miRNAs in combination depicted the best-fit model in relation to disease severity (PASI) compared with individual miRNAs, with the highest R2 value of 0.94 and the lowest AIC score of 131.8. Each of the miRNAs also exhibited a significant association with at least one of the other miRNAs in the panel. Importantly, the five miRNAs in the panel regulate one or more immune-inflammation pathways based on target prediction, pathway network analysis, and validated roles in the literature. The miRNA panel provides a rationalized combination of biomarkers that can be tested further on an expanded cohort of patients for their diagnostic value.

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Section: Resultsmentioning

confidence: 99%

A panel of blood-based circulatory miRNAs with diagnostic potential in patients with psoriasis

Madaan,

Sharma,

Tyagi

et al. 2023

Front. Med.

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“…Second, although DYRK1A inhibitors have exhibited strong anti-diabetic potential in vivo and in vitro, these compounds face severe challenges. DYRK1A is widely distributed in various tissues throughout the body, and can play a critical role in a variety of biological processes including cell survival and proliferation, such as B-cell survival [ 95 , 96 ], HaCaT cell proliferation [ 97 ], the development and aging of the central nervous system (CNS) [ 98 ], and lipid metabolism [ 99 ] Therefore, we must address the problem to enhance the selectivity of compounds for islet β-cells. Taking EGCG as an example, this can easily pass the blood–brain barrier and exert pharmacological effects on the central nervous system, which is an important obstacle to their further study in the field of diabetic therapeutics.…”

Section: Discussionmentioning

confidence: 99%

Regeneration of Pancreatic β-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors

Guo

Yao

et al. 2022

Metabolites

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The pathogenesis of diabetes mellitus is characterized by insulin resistance and islet β-cell dysfunction. Up to now, the focus of diabetes treatment has been to control blood glucose to prevent diabetic complications. There is an urgent need to develop a therapeutic approach to restore the mass and function of β-cells. Although exogenous islet cell transplantation has been used to help patients control blood glucose, it is costly and has very narrow application scenario. So far, small molecules have been reported to stimulate β-cell proliferation and expand β-cell mass, increasing insulin secretion. Dual-specificity tyrosine-regulated kinase 1A (DYRK1A) inhibitors can induce human β-cell proliferation in vitro and in vivo, and show great potential in the field of diabetes therapeutics. From this perspective, we elaborated on the mechanism by which DYRK1A inhibitors regulate the proliferation of pancreatic β-cells, and summarized several effective natural DYRK1A inhibitors, hoping to provide clues for subsequent structural optimization and drug development in the future.

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“…FOXM1 expression in the lesions was reduced by about two-fold after miR-214-3p application. Liu et al [ 63 ] indicated the downregulation of miR-215-5p in cytokine-stimulated HaCaT and imiquimod-treated skin tissue. The treatment of miR-215-5p agomirs on imiquimod-treated mice decreased the number of Ki67-positive cells in the epidermis.…”

Section: Mirnas For Treating Inflammatory Skin Diseasesmentioning

confidence: 99%

Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases

et al. 2022

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Skin inflammation occurs due to immune dysregulation because of internal disorders, infections, and allergic reactions. The inflammation of the skin is a major sign of chronic autoimmune inflammatory diseases, such as psoriasis, atopic dermatitis (AD), and lupus erythematosus. Although there are many therapies for treating these cutaneous inflammation diseases, their recurrence rates are high due to incomplete resolution. MicroRNA (miRNA) plays a critical role in skin inflammation by regulating the expression of protein-coding genes at the posttranscriptional level during pathogenesis and homeostasis maintenance. Some miRNAs possess anti-inflammatory features, which are beneficial for mitigating the inflammatory response. miRNAs that are reduced in inflammatory skin diseases can be supplied transiently using miRNA mimics and agomir. miRNA-based therapies that can target multiple genes in a given pathway are potential candidates for the treatment of skin inflammation. This review article offers an overview of the function of miRNA in skin inflammation regulation, with a focus on psoriasis, AD, and cutaneous wounds. Some bioactive molecules can target and modulate miRNAs to achieve the objective of inflammation suppression. This review also reports the anti-inflammatory efficacy of these molecules through modulating miRNA expression. The main limitations of miRNA-based therapies are rapid biodegradation and poor skin and cell penetration. Consideration was given to improving these drawbacks using the approaches of cell-penetrating peptides (CPPs), nanocarriers, exosomes, and low-frequency ultrasound. A formulation design for successful miRNA delivery into skin and target cells is also described in this review. The possible use of miRNAs as biomarkers and therapeutic modalities could open a novel opportunity for the diagnosis and treatment of inflammation-associated skin diseases.

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MicroRNA‐215‐5p inhibits the proliferation of keratinocytes and alleviates psoriasis‐like inflammation by negatively regulating DYRK1A and its downstream signalling pathways

Cited by 11 publications

References 38 publications

A panel of blood-based circulatory miRNAs with diagnostic potential in patients with psoriasis

A panel of blood-based circulatory miRNAs with diagnostic potential in patients with psoriasis

Regeneration of Pancreatic β-Cells for Diabetes Therapeutics by Natural DYRK1A Inhibitors

Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases

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