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Updated: May 17, 2025
Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
Published on: July 14, 2017
Hsa-miR-31-3p targets CLDN8 to compromise skin barrier integrity in psoriasis
Yunhua Tu1,2, Li Wang1, Lijun An2
1Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, China.
Abstract:
Skin barrier dysfunction in psoriasis has emerged as a significant concern, yet the underlying molecular mechanisms remain incompletely understood. This study investigates the role of hsa-miR-31-3p in regulating skin barrier function through its interaction with claudin-8 (CLDN8) in psoriasis. Through analysis of clinical samples and public datasets, we observed significantly impaired skin barrier function in psoriasis patients, characterized by increased transepidermal water loss and decreased stratum corneum hydration. Notably, CLDN8 expression was markedly downregulated in psoriatic lesions, while hsa-miR-31-3p levels were elevated. Bioinformatics analysis and molecular studies revealed that hsa-miR-31-3p directly targets the 3'UTR of CLDN8, leading to its downregulation. In vitro experiments demonstrated that both CLDN8 knockdown and hsa-miR-31-3p overexpression compromised the permeability barrier in keratinocytes. Furthermore, in an imiquimod-induced psoriasis mouse model, administration of mmu-miR-31-3p antagomir effectively ameliorated skin barrier damage, reduced inflammatory manifestations, and restored CLDN8 expression. These findings unveil a novel mechanism whereby hsa-miR-31-3p regulates skin barrier function through CLDN8 in psoriasis, suggesting potential therapeutic strategies targeting this pathway for psoriasis treatment.
Insights
Psoriasis involves skin barrier defects. This study shows microRNA-31 (miR-31) impairs skin barrier by downregulating claudin-8 (CLDN8), offering a new therapeutic target for psoriasis.
Area of Science:
- Dermatology
- Molecular Biology
- Genetics
Background:
- Skin barrier dysfunction is a key feature of psoriasis.
- The molecular regulators of this dysfunction are not fully understood.
- Claudin-8 (CLDN8) is crucial for skin barrier integrity.
Purpose of the Study:
- To investigate the role of hsa-miR-31-3p in regulating skin barrier function in psoriasis.
- To elucidate the interaction between hsa-miR-31-3p and claudin-8 (CLDN8) in the context of psoriasis.
- To explore potential therapeutic strategies targeting the miR-31/CLDN8 pathway.
Main Methods:
- Analysis of clinical psoriasis samples and public datasets.
- Bioinformatics analysis to predict miRNA-target interactions.
- In vitro studies using keratinocytes (CLDN8 knockdown and miR-31 overexpression).
- In vivo studies using an imiquimod-induced psoriasis mouse model and antagomir treatment.
Main Results:
- Psoriasis patients exhibit impaired skin barrier function (increased transepidermal water loss, decreased hydration).
- CLDN8 expression is reduced, while hsa-miR-31-3p is elevated in psoriatic lesions.
- hsa-miR-31-3p directly targets CLDN8, leading to its downregulation and compromised keratinocyte barrier function.
- Antagomir treatment in a mouse model improved skin barrier, reduced inflammation, and restored CLDN8 levels.
Conclusions:
- hsa-miR-31-3p plays a critical role in regulating skin barrier function in psoriasis by downregulating CLDN8.
- The miR-31/CLDN8 pathway represents a novel mechanism contributing to psoriasis pathogenesis.
- Targeting hsa-miR-31-3p offers a potential therapeutic avenue for psoriasis treatment.
