C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis
Abstract Dupuytren’s contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signallin...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-11-01
|
| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05558-8 |
| _version_ | 1797557242094944256 |
|---|---|
| author | Atsushi Goto Shingo Komura Koki Kato Rie Maki Akihiro Hirakawa Hiroyuki Tomita Akihiro Hirata Yasuhiro Yamada Haruhiko Akiyama |
| author_facet | Atsushi Goto Shingo Komura Koki Kato Rie Maki Akihiro Hirakawa Hiroyuki Tomita Akihiro Hirata Yasuhiro Yamada Haruhiko Akiyama |
| author_sort | Atsushi Goto |
| collection | DOAJ |
| description | Abstract Dupuytren’s contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren’s contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren’s contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell–macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell–macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis. |
| first_indexed | 2024-03-10T17:14:33Z |
| format | Article |
| id | doaj.art-d005b1ca92834f8ba074982c1564d462 |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-10T17:14:33Z |
| publishDate | 2023-11-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-d005b1ca92834f8ba074982c1564d4622023-11-20T10:34:14ZengNature PortfolioCommunications Biology2399-36422023-11-016111610.1038/s42003-023-05558-8C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosisAtsushi Goto0Shingo Komura1Koki Kato2Rie Maki3Akihiro Hirakawa4Hiroyuki Tomita5Akihiro Hirata6Yasuhiro Yamada7Haruhiko Akiyama8Department of Orthopaedic Surgery, Gifu University Graduate School of MedicineDepartment of Orthopaedic Surgery, Gifu University Graduate School of MedicineDepartment of Orthopaedic Surgery, Gifu University Graduate School of MedicineDepartment of Orthopaedic Surgery, Gifu University Graduate School of MedicineDepartment of Orthopaedic Surgery, Gifu University Graduate School of MedicineDepartment of Tumor Pathology, Gifu University Graduate School of MedicineLaboratory of Veterinary Pathology, Joint Department of Veterinary Medicine, Faculty of Applied Biological Sciences, Gifu UniversityDepartment of Molecular Pathology, Graduate School of Medicine, The University of TokyoDepartment of Orthopaedic Surgery, Gifu University Graduate School of MedicineAbstract Dupuytren’s contracture, a superficial dermal fibrosis, causes flexion contracture of the affected finger, impairing hand function. Specific single-nucleotide polymorphisms within genes in the Wnt signalling pathway are associated with the disease. However, the precise role of Wnt signalling dysregulation in the onset and progression of Dupuytren’s contracture remains unclear. Here, using a fibrosis mouse model and clinical samples of human Dupuytren’s contractures, we demonstrate that the activation of Wnt/β-catenin signalling in Tppp3-positive cells in the dermis of the paw is associated with the development of fibrosis. Fibrosis development and progression via Wnt/β-catenin signalling are closely related to stromal cell–macrophage interactions, and Wnt/β-catenin signalling activation in Tppp3-positive stromal cells causes M2 macrophage infiltration via chemokine Cxcl14, resulting in the formation of a TGF-β-expressing fibrotic niche. Inhibition of Cxcl14 mitigates fibrosis by decreasing macrophage infiltration. These findings suggest that Cxcl14-mediated stromal cell–macrophage interaction is a promising therapeutic target for Wnt/β-catenin-induced fibrosis.https://doi.org/10.1038/s42003-023-05558-8 |
| spellingShingle | Atsushi Goto Shingo Komura Koki Kato Rie Maki Akihiro Hirakawa Hiroyuki Tomita Akihiro Hirata Yasuhiro Yamada Haruhiko Akiyama C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis Communications Biology |
| title | C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis |
| title_full | C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis |
| title_fullStr | C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis |
| title_full_unstemmed | C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis |
| title_short | C-X-C domain ligand 14-mediated stromal cell–macrophage interaction as a therapeutic target for hand dermal fibrosis |
| title_sort | c x c domain ligand 14 mediated stromal cell macrophage interaction as a therapeutic target for hand dermal fibrosis |
| url | https://doi.org/10.1038/s42003-023-05558-8 |
| work_keys_str_mv | AT atsushigoto cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT shingokomura cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT kokikato cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT riemaki cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT akihirohirakawa cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT hiroyukitomita cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT akihirohirata cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT yasuhiroyamada cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis AT haruhikoakiyama cxcdomainligand14mediatedstromalcellmacrophageinteractionasatherapeutictargetforhanddermalfibrosis |