Targeting
            <i>miR-21</i>
            to Treat Psoriasis

Guinea-Viniegra, Juan; Jiménez, María; Schönthaler, Helia B.; Navarro, R.; Delgado, Yolanda Núñez; Concha-Garzón, M.J.; Tschachler, Erwin; Obad, Susanna; Daudén, E.; Wagner, Erwin F.

doi:10.1126/scitranslmed.3008089

Cited by 130 publications

(140 citation statements)

References 32 publications

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“…Since TACE mRNA levels were not elevated in K5.Stat3C mice, this finding suggested that Stat3 signaling contributed to enhanced TACE activity via post-transcriptional regulation. Most recently, it has been reported that microRNA-21 (miR-21) targeted TIMP-3 and was functionally involved in the pathogenesis of psoriasis [51]. Most interestingly, miR-21 expression was up-regulated by the Stat3 signaling [52], supporting our data using K5.Stat3C keratinocytes, which showed acute decline of TIMP-3 upon TPA treatment, thereby TACE activity might be elevated, followed by release of the TACE substrates.…”

Section: Discussionsupporting

confidence: 87%

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

et al. 2014

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TNF-α plays a crucial role in psoriasis; therefore, TNF inhibition has become a gold standard for the treatment of psoriasis. TNF-α is processed from a membrane-bound form by TNF-α converting enzyme (TACE) to soluble form, which exerts a number of biological activities. EGF receptor (EGFR) ligands, including heparin-binding EGF-like growth factor (HB-EGF), amphiregulin and transforming growth factor (TGF)-α are also TACE substrates and are psoriasis-associated growth factors. Vascular endothelial growth factor (VEGF), one of the downstream molecules of EGFR and TNF signaling, plays a key role in angiogenesis for developing psoriasis. In the present study, to assess the possible role of TACE in the pathogenesis of psoriasis, we investigated the involvement of TACE in TPA-induced psoriasis-like lesions in K5.Stat3C mice, which represent a mouse model of psoriasis. In this mouse model, TNF-α, amphiregulin, HB-EGF and TGF-α were significantly up-regulated in the skin lesions, similar to human psoriasis. Treatment of K5.Stat3C mice with TNF-α or EGFR inhibitors attenuated the skin lesions, suggesting the roles of TACE substrates in psoriasis. Furthermore, the skin lesions of K5.Stat3C mice showed down-regulation of tissue inhibitor of metalloproteinase-3, an endogenous inhibitor of TACE, and an increase in soluble TNF-α. A TACE inhibitor abrogated EGFR ligand-dependent keratinocyte proliferation and VEGF production in vitro, suggesting that TACE was involved in both epidermal hyperplasia and angiogenesis during psoriasis development. These results strongly suggest that TACE contributes to the development of psoriatic lesions through releasing two kinds of psoriasis mediators, TNF-α and EGFR ligands. Therefore, TACE could be a potential therapeutic target for the treatment of psoriasis.

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Section: Discussionsupporting

confidence: 87%

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

et al. 2014

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“…ROS‐mediated apoptosis induction in AML (THP‐1) is low due to defects in p38‐dependent downstream signaling, and we here strived to further decipher the redox signaling that possibly contribute to this resistance in order to find new targets for AML treatment. Several reports demonstrated that AP‐1 factors in both, the innate (THP‐1) and the adaptive immune system (Jurkat) have important roles in human diseases and cancer . AP‐1 subunits, such as JUN, JUND, and FOS, are important for cell fate decisions, and their phosphorylation is often regulated by mitogen‐activated (MAP) kinases, for example, Jnk and p38 .…”

Section: Resultsmentioning

confidence: 99%

Redox‐regulation of activator protein 1 family members in blood cancer cell lines exposed to cold physical plasma‐treated medium

Schmidt

Rödder

Hasse

et al. 2016

Plasma Processes & Polymers

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Targeting cancer cells with cold physical plasma emerged as a promising application in plasma medicine. To understand its mode of action with regard to cellular redox‐regulation, two leukemia cell lines (Jurkat and THP‐1 cells) were plasma‐treated and their gene expression was compared. Transcriptomics revealed strikingly similar expression levels of activator protein 1 family members, and of a particular set of genes associated with apoptosis, DNA repair, and antioxidant defense. Interestingly, important constitutively expressed antioxidant transcripts were differently expressed in both cell types which suggest them to be crucial for the Jurkat's high and the THP‐1 cells’ low sensitivity to plasma. Utilizing these targets as biological read outs may help rendering plasmas more effective against different types of cancers.

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“…Guinea-Viniefar et al demonstrated that the inhibition of miR-21 ameliorated disease pathology in patient-derived psoriatic skin xenotransplants in mice and in a psoriasis-like mouse model [34]. Zhao et al reported that the down-regulation of miR-210 improves immune dysfunction in CD4 + T cells of psoriasis patients [35].…”

Section: Discussionmentioning

confidence: 97%

MicroRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis

et al. 2015

Immunology Letters

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Targeting miR-21 to Treat Psoriasis

Cited by 130 publications

References 32 publications

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

Involvement of TNF-α Converting Enzyme in the Development of Psoriasis-Like Lesions in a Mouse Model

Redox‐regulation of activator protein 1 family members in blood cancer cell lines exposed to cold physical plasma‐treated medium

MicroRNA-138 regulates the balance of Th1/Th2 via targeting RUNX3 in psoriasis

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