ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
Cinobufagin Directly Targets PDE4D to Disrupt Fibroblast-Dendritic Cell Crosstalk in Atopic Dermatitis.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The trial behind it
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Who cites it
3 citing papers in PubMed.
- Cinobufagin as a Potential Intervention Against Liver Cancer-A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Engineering Multi-Scale Transdermal Delivery Systems for Atopic Dermatitis: Emerging Insights from the Gut-Skin Axis.International journal of nanomedicine · 2026Review
- Cinobufagin Directly Targets PDE4D to Disrupt Fibroblast-Dendritic Cell Crosstalk in Atopic Dermatitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
Corrections and comments
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Authors and funding
15 authors.
Funding
Abstract
Atopic dermatitis (AD) is a chronic inflammatory skin disease driven by immune dysregulation and Th2-dominant inflammation. This study identifies phosphodiesterase 4D (PDE4D) as a key regulator of AD pathogenesis and a potential therapeutic target. Single-cell RNA sequencing (scRNA-seq) revealed activation of the macrophage migration inhibitory factor (MIF) signaling pathway in lesional tissues, with inflammatory fibroblasts mediating MIF-driven interactions with myeloid cells. Elevated PDE4D expression in lesional tissues suppressed cyclic adenosine monophosphate (cAMP) signaling, promoting inflammation. Cinobufagin, a bufadienolide compound, is identified as a potent PDE4D inhibitor. Compared to other PDE4 inhibitors used in clinical cases, cinobufagin demonstrated superior efficacy in improving AD in mice while effectively regulating the MIF pathway. It directly bound to PDE4D, restored cAMP signaling, suppressed MIF secretion in inflammatory fibroblasts, and disrupted fibroblast-dendritic cell interactions via the cAMP/protein kinase A (PKA)/cAMP-response element binding protein (CREB) pathway, thereby significantly reducing the clinical and histological features of AD. Notably, PDE4D knockout mice exhibited diminished inflammation, mimicking the effects of cinobufagin and confirming a role for PDE4D in AD progression. These findings establish PDE4D as a critical driver of AD and demonstrate that cinobufagin effectively targets this pathway, offering a promising therapeutic approach for AD and related inflammatory skin disorders.
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Registered trials
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 Socratic graph.