ArticleArthritis & rheumatology (Hoboken, N.J.)2023
Regulation of Photosensitivity by the Hippo Pathway in Lupus Skin.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 17 citations in OpenAlex.
- Myeloid infiltration and epidermal dysregulation characterize cutaneous photosensitivity in systemic lupus erythematosus.Science translational medicine · 2026Article
- Fractional Subnanosecond Nd:YAG Laser Improves Matrix Architecture in Ultraviolet-Aged Facial Retaining Ligaments in Rats.International journal of molecular sciences · 2026Article
- Effects of LATS1/2 kinases inhibition on lung epithelial cells in a regeneration model.Molecular and cellular biochemistry · 2026Article
- Persistent cutaneous lupus erythematosus: A pathway toward systemic disease?Journal of translational autoimmunity · 2026Review
- Unraveling the complexity of skin's biological aging utilizing epigenetic clocks.Clinical epigenetics · 2026Article
- An intelligent nanoliposome alleviates disc degeneration and discogenic pain by inhibiting neurovascular ingrowth via a "Soil-conditioning, seed-modulating, and weeds-suppressing" strategy.Bioactive materials · 2026Article
- The Role of Vitamin D in Autoimmune Diseases.International journal of molecular sciences · 2026Review
- Epigenetic reprogramming in autoimmune and immune-mediated skin disease.Frontiers in immunology · 2026Review
- Cutaneous lupus erythematosus - from pathogenesis to targeted therapy.Nature reviews. Rheumatology · 2025Review
- Dysregulation in keratinocytes drives systemic lupus erythematosus onset.Cellular & molecular immunology · 2025Article
- Narrowband ultraviolet B radiation attenuates nucleus pulposus pyroptosis to ameliorate intervertebral disc degeneration by activating NRF2/KEAP1 antioxidant pathway.Frontiers in immunology · 2025Article
- Plasma cell-free DNA genome-wide methylation profiling enables detection and activity assessment in systemic lupus erythematosus.Frontiers in immunology · 2025Article
- Keratinocytes - Amplifiers of Immune Responses in Systemic Lupus Erythematosus.Current rheumatology reports · 2024Review
- An improved TEAD dominant-negative protein inhibitor to study Hippo YAP1/TAZ-dependent transcription.bioRxiv : the preprint server for biology · 2024Article
- American College of Rheumatology White Paper: The Effects of Climate Change on Rheumatic Conditions-An Evolving Landscape and a Path Forward.Arthritis & rheumatology (Hoboken, N.J.) · 2024Review
- Research progress on Hippo signaling pathway effector molecules in rheumatic immune system diseases.Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences · 2024Review
- HERC6 regulates STING activity in a sex-biased manner through modulation of LATS2/VGLL3 Hippo signaling.iScience · 2024Article
- Serum Metabolomics Analysis of Skin-Involved Systemic Lupus Erythematosus: Association of Anti-SSA Antibodies with Photosensitivity.Journal of inflammation research · 2023Article
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
objectivePhotosensitivity is one of the most common manifestations of systemic lupus erythematosus (SLE), yet its pathogenesis is not well understood. The normal-appearing epidermis of patients with SLE exhibits increased ultraviolet B (UVB)-driven cell death that persists in cell culture. Here, we investigated the role of epigenetic modification and Hippo signaling in enhanced UVB-induced apoptosis seen in SLE keratinocytes.
methodsWe analyzed DNA methylation in cultured keratinocytes from SLE patients compared to keratinocytes from healthy controls (n = 6/group). Protein expression was validated in cultured keratinocytes using immunoblotting and immunofluorescence. An immortalized keratinocyte line overexpressing WWC1 was generated via lentiviral vector. WWC1-driven changes were inhibited using a large tumor suppressor kinase 1/2 (LATS1/2) inhibitor (TRULI) and small interfering RNA (siRNA). The interaction between the Yes-associated protein (YAP) and the transcriptional enhancer associate domain (TEAD) was inhibited by overexpression of an N/TERT cell line expressing a tetracycline-inducible green fluorescent protein-tagged protein that inhibits YAP-TEAD binding (TEADi). Apoptosis was assessed using cleaved caspase 3/7 and TUNEL staining.
resultsHippo signaling was the top differentially methylated pathway in SLE versus control keratinocytes. SLE keratinocytes (n = 6) showed significant hypomethylation (Δβ = -0.153) and thus overexpression of the Hippo regulator WWC1 (P = 0.002). WWC1 overexpression increased LATS1/2 kinase activation, leading to YAP cytoplasmic retention and altered proapoptotic transcription in SLE keratinocytes. Accordingly, UVB-mediated apoptosis in keratinocytes could be enhanced by WWC1 overexpression or YAP-TEAD inhibition, mimicking SLE keratinocytes. Importantly, inhibition of LATS1/2 with either the chemical inhibitor TRULI or siRNA effectively eliminated enhanced UVB-apoptosis in SLE keratinocytes.
conclusionOur work unravels a novel driver of photosensitivity in SLE: overactive Hippo signaling in SLE keratinocytes restricts YAP transcriptional activity, leading to shifts that promote UVB apoptosis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.