LncRNA-WAKMAR2 regulates expression of CLDN1 to affect skin barrier through recruiting c-Fos
Yunhua Tu1,2, Li Wang1, Xiaoli Wang3
1Department of Dermatology, First Affiliated Hospital of Kunming Medical University, Kunming, China.
Background:
Chronic actinic dermatitis (CAD) is an immune-mediated photo-allergic skin disease. In the clinic, the treatment of this disease is hampered by the lack of proper understanding of the skin barrier dysfunction mechanism.
Objective:
To illuminate the mechanism of skin barrier dysfunction in CAD.
Methods:
Transcriptome sequencing and protein profiling were used to detect skin barrier injury-related genes. RNA pull down, a promoter-reporter gene assay, and chromatin isolation by RNA purification-sequencing were used to elucidate the effect of WAKMAR2 in skin barrier functionality.
Results:
Transcriptome sequencing from patient's tissues showed a significantly decreased expression of WAKMAR2. Down-regulation of WAKMAR2 destroyed the keratinocyte barrier. Moreover, WAKMAR2 can directly bind to the c-Fos protein. This novel long non-coding RNA (LncRNA)-protein complexes were targeted to the CLDN1 promotor. Overexpression of WAKMAR2 enhanced the promoter activity of CLDN1, while the addition of AP-1 inhibitor could reverse this phenomenon. Furthermore, our in vivo results suggested that expression of WAKMAR2 was required for the repair of skin damage in mice induced by ultraviolet irradiation.
Conclusions:
We identified a crucial LncRNA (WAKMAR2) for the protection of the skin barrier in vitro and in vivo. Mechanically, it can specifically interact with c-Fos protein for the regulation of CLDN1, a finding which could be applied for CAD treatment.
Insights
Researchers identified a long non-coding RNA (LncRNA), WAKMAR2, crucial for skin barrier protection in chronic actinic dermatitis (CAD). WAKMAR2 interacts with c-Fos to regulate CLDN1, offering a potential therapeutic target for CAD.
Area of Science:
- Dermatology
- Molecular Biology
- Immunology
Background:
- Chronic actinic dermatitis (CAD) is an immune-mediated photosensitive skin condition.
- Current treatment is limited by poor understanding of skin barrier dysfunction in CAD.
Purpose of the Study:
- To elucidate the mechanism of skin barrier dysfunction in CAD.
- To identify key molecular players involved in CAD pathogenesis.
Main Methods:
- Transcriptome sequencing and protein profiling to identify skin barrier injury-related genes.
- RNA pull down, promoter-reporter gene assays, and ChIP-seq to investigate WAKMAR2 function.
- In vitro and in vivo models to assess WAKMAR2's role in skin barrier integrity.
Main Results:
- Significantly decreased WAKMAR2 expression observed in CAD patient tissues.
- WAKMAR2 down-regulation impairs keratinocyte barrier function.
- WAKMAR2 directly binds c-Fos, forming a complex that targets the CLDN1 promoter, enhancing its activity.
- WAKMAR2 is essential for skin damage repair following UV irradiation in vivo.
Conclusions:
- WAKMAR2 is a critical long non-coding RNA (LncRNA) for maintaining skin barrier integrity, both in vitro and in vivo.
- WAKMAR2's interaction with c-Fos regulates CLDN1, presenting a novel therapeutic avenue for CAD treatment.
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