Single cell deciphering of pruritic keloids: the interaction between fibroblasts and Schwann cells through the Midkine signaling Article Swipe
En Yang
,
Ruoqing Xu
,
Liying Tu
,
Hanrui Zhang
,
Shenying Luo
,
Hsin Liang
,
Yunhan Liu
,
Shuchen Gu
,
Yixuan Zhao
,
Xin Huang
,
Tao Zan
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/burnst/tkaf057
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1093/burnst/tkaf057
Background Keloids are a common skin fibroproliferative disease that can result in severe aesthetic and functional concerns. Pruritus and pain are the most prevalent clinical manifestations of keloids. Schwann cells (SCs) variation and neuropathy within keloids contribute to these uncomfortable sensations; however the underlying mechanisms remain unclear. This study aims to explore the potential role of fibroblasts (FBs) and SCs in pruritic and pain keloids. Methods The activity of FBs and SCs was investigated using single-cell RNA sequencing (scRNA-seq) data of keloids. These bioinformatics analysis results were validated through in vitro cell culture, clinical samples, and in vivo experiments. The selected molecule was confirmed to be correlated with pain and itch and was subsequently used to treat cells in order to investigate its role in keloids. The in vivo inhibition assay was performed to evaluate its therapeutic potential. Results Our scRNA-seq analysis identified specific types of FBs and SCs were present in higher proportions in keloids and exhibited neurogenesis-related functions. Upon conducting an interaction analysis of these two cell types, we identified a critical molecule, Midkine (MDK), which is positively correlated with the patients’ pain and itching levels. Besides, MDK treatment facilitated the proliferation of SCs and their transition to a repairing phenotype, resulting in neuronal axonogenesis. This activation of repairing SCs promoted the release of substance P from nerve fibers, leading to clinical symptoms of pain and pruritus in keloid patients. Targeting MDK effectively reduces abnormal Schwann cell proliferation and subsequently inhibits the secretion of neuropeptides that trigger pain and pruritus. Conclusions Our study uncovered the interaction between FBs and SCs in the development of keloidal pain and pruritus, offering a novel therapeutic strategy to alleviate the distressing symptoms of keloids.
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- article
- Language
- en
- Landing Page
- https://doi.org/10.1093/burnst/tkaf057
- https://academic.oup.com/burnstrauma/advance-article-pdf/doi/10.1093/burnst/tkaf057/64460105/tkaf057.pdf
- OA Status
- diamond
- References
- 52
- OpenAlex ID
- https://openalex.org/W4414701704
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4414701704Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1093/burnst/tkaf057Digital Object Identifier
- Title
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Single cell deciphering of pruritic keloids: the interaction between fibroblasts and Schwann cells through the Midkine signalingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
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2025Year of publication
- Publication date
-
2025-01-01Full publication date if available
- Authors
-
En Yang, Ruoqing Xu, Liying Tu, Hanrui Zhang, Shenying Luo, Hsin Liang, Yunhan Liu, Shuchen Gu, Yixuan Zhao, Xin Huang, Tao ZanList of authors in order
- Landing page
-
https://doi.org/10.1093/burnst/tkaf057Publisher landing page
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https://academic.oup.com/burnstrauma/advance-article-pdf/doi/10.1093/burnst/tkaf057/64460105/tkaf057.pdfDirect link to full text PDF
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YesWhether a free full text is available
- OA status
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diamondOpen access status per OpenAlex
- OA URL
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https://academic.oup.com/burnstrauma/advance-article-pdf/doi/10.1093/burnst/tkaf057/64460105/tkaf057.pdfDirect OA link when available
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