Inhibiting HuR-Mediated mRNA Stabilization Attenuates Psoriasis-Like Inflammation in Preclinical Models
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Le résumé fourni par la source
Purpose: Psoriasis is a chronic inflammatory skin disease characterized by hyperproliferative keratinocytes and activated Th17/Th1 lymphocytes, which sustain a self-perpetuating cycle by releasing pro-inflammatory cytokines. The RNA-binding protein (RBP) Human Antigen R (HuR) stabilizes many of these cytokine mRNAs, contributing to disease progression. This study aims to investigate the role of the HuR protein in psoriasis and modulate its activity to develop novel therapeutic strategies. Patients and Methods: We evaluated the effects of Human Antigen R (HuR) silencing on psoriatic markers in both patient-derived keratinocytes and lymphocytes. Furthermore, we identified novel HuR targets within a psoriatic context using enhanced Cross-Linking and ImmunoPrecipitation sequencing (eCLIP-seq) in psoriasis-like HaCaT cells. Finally, we investigated the pharmacological effects of the TM11, a Tanshinone-mimic (TM) molecule, in an in vivo mouse model and an ex vivo 3D human skin model. Results: Studies on HuR function in HaCaT cells and in patient-derived primary keratinocytes and lymphocytes, demonstrated that keratinocyte proliferation and lymphocyte activation and differentiation are both dependent on HuR. In psoriatic-like HaCaT cells, eCLIP-seq data identified novel psoriatic-related HuR targets, and its mRNA-stabilizing activity was confirmed. Treatment with TM11, that competes with HuR-mRNA binding, reduced keratinocyte proliferation and psoriasis proteins (Cyclin B, Survivin, S100A7, eFABP), and almost suppressed T-cell activation (CD25⁺CD69⁺) and Th17/Th1 cytokine production. In vivo, TM11 reduced psoriasis-like symptoms in Imiquimod-treated mice, reducing Psoriasis Area and Severity Index (PASI) scores, systemic inflammation and histological alterations. In ex vivo InflammaSkin ® models, TM11 restored epidermal morphology, decreased Ki-67 positive cells and lowered IL17AF and IFN-γ secretion. Conclusion: Overall, these findings highlight HuR as a key driver of psoriasis pathogenesis and provide preclinical evidence that pharmacological modulation of HuR activity, by TM11 treatment, could provide a conceptual therapeutic rationale for psoriasis, potentially contributing to the reduction of keratinocyte hyperproliferation and immune activation while favouring the restoration of skin homeostasis. However, further preclinical and clinical validation will be required to establish its translational feasibility. Keywords: RBP, TMs, primary cells, in-vivo, ex-vivo
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Inhibiting HuR-Mediated mRNA Stabilization Attenuates Psoriasis-Like Inflammation in Preclinical Models
- Date Crossref
- 01/09/2026
- Éditeur
- Informa UK Limited
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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University of Trento Department of Cellular pays non établi dans la noticeUniversité ou école supérieure
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University of Modena and Reggio Emilia Department of Medical and Surgical Sciences pays non établi dans la noticeUniversité ou école supérieure
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Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico Unit of Cell and Gene Therapies pays non établi dans la noticeÉtablissement de santé
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Azienda Ospedaliero-Universitaria di Modena pays non établi dans la noticeÉtablissement de santé
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University of Milan Department of Pathophysiology and Transplantation pays non établi dans la noticeUniversité ou école supérieure
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Tecnologie Avanzate (Italy) pays non établi dans la noticeEntreprise
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Clinical Pathology Flow Cytometry Facility pays non établi dans la noticeÉtablissement de santé
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AOU Policlinico di Modena Dermatology pays non établi dans la noticeÉtablissement de santé
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Istituto di Scienze e Tecnologie Chimiche (SCITEC) 'Giulio Natta' pays non établi dans la noticeInstitution
Department of Cellular — University of Trento, Department of Medical and Surgical Sciences — University of Modena and Reggio Emilia et Unit of Cell and Gene Therapies — Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, avec 6 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.