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Updated: Sep 22, 2025
04:59
Cheek Injection Model for Simultaneous Measurement of Pain and Itch-related Behaviors
Published on: September 27, 2019
12.4K
The PLAUR signaling promotes chronic pruritus
Weiwei Chen1, Yanqing Li1, Martin Steinhoff2,3,4,5,6,7
1School of Life Sciences, Henan University, Kaifeng, China.
Summary
Chronic itch involves Serpin E1 signaling through its receptor PLAUR, which activates TLR2 pathways. This pathway promotes skin inflammation and itch, potentially worsening conditions like atopic dermatitis.
Area of Science:
- Dermatology and Neuroscience
- Molecular Biology and Immunology
Background:
- Chronic itch, common in atopic dermatitis (AD) and psoriasis, involves Serpin E1, but its receptor and signaling pathways remain unclear.
- Understanding the molecular mechanisms of chronic itch is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the clinical relevance of the potential Serpin E1 receptor, PLAUR, in chronic itch.
- To elucidate the neuro-cutaneous Serpin E1-PLAUR signaling pathways involved in skin inflammation and itch.
Main Methods:
- Analysis of PLAUR expression in human lesional AD and psoriasis skin specimens.
- Investigation of Serpin E1-PLAUR interaction in sensory neurons of AD-like murine models.
- Assessment of TLR2 activation, gene expression (BNP, OSM, PAR2), and protein release (G-CSF, IL-8).
- Evaluation of Serpin E1 inhibitor efficacy on itch, inflammation, and gene expression in vivo.
Main Results:
- PLAUR is overexpressed in lesional skin of human AD and psoriasis, and in sensory neurons of murine AD models.
- Serpin E1 binding to PLAUR on sensory neurons upregulates TLR2 and co-signaling proteins, promoting itch and inflammation-related gene transcription.
- OSM, induced by this pathway, triggers acute itch and cytokine release, while a Serpin E1 inhibitor reduces itch and inflammation markers.
Conclusions:
- The PLAUR-TLR2-OSM signaling axis facilitates skin-nerve communication, driving cutaneous inflammation and chronic itch.
- This pathway contributes significantly to the exacerbation of atopic dermatitis and amplified itch circuits.
- Targeting Serpin E1-PLAUR signaling presents a potential therapeutic strategy for managing chronic itch in skin diseases.
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