{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T01:43:09Z","timestamp":1789609389358,"version":"build-2803163510"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T00:00:00Z","timestamp":1773964800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82103606"],"award-info":[{"award-number":["82103606"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82403618"],"award-info":[{"award-number":["82403618"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology","award":["2025A28"],"award-info":[{"award-number":["2025A28"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Keloid formation is a chronic inflammatory skin disease, characterized by abnormal fibroproliferative scars. There are no effective treatments. Many factors are involved in keloid formation, primarily a highly active inflammatory response, wound tension and hereditary susceptibility. Collagen signalling plays important roles in various diseases, including fibrotic diseases and tumours, but its function in keloid inflammation remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To study the roles and mechanisms of collagen signalling in inflammation development during keloid formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Normal and keloid keratinocytes along with fibroblasts were isolated from fresh normal skin and keloid tissues. Picrosirius red staining, Western blotting, quantitative polymerase chain reaction, co-immunoprecipitation, APEX2-mediated proximity biotinylation, enzyme-linked immunosorbent assay, immunohistochemistry and immunofluorescence were used to discover the roles of collagen I-discoidin domain receptor 1 (DDR1) signalling in the development of inflammation. Human keloid samples were subcutaneously transplanted onto nude mice to build a keloid xenograft model. The therapeutic potential of a DDR1 inhibitor (7rh) and an ADP-ribosylation factor 6 (ARF6) inhibitor (NAV-2729) was examined in keloid inflammation development.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In keloid tissue, we found significant elevation of both phosphorylated nuclear factor kappa B (NF-\u03baB) and signal transducer and activator of transcription 3 (STAT3). In keloid tissue: (i) collagen I was upregulated and comprised the vast proportion of collagen types; (ii) collagen I signalling promoted activation of the keloid inflammation amplifier by DDR1; (iii)\u00a0DDR1 and ARF6 were upregulated, and their levels positively correlated with each other; (iv) elevated DDR1 was mainly expressed in fibroblasts, in keloid dermal tissues; (v) collagen I-DDR1 signalling activated NF\u03baB and STAT3 signalling; and (vi)\u00a0in the keloid xenograft model, 7rh restrained keloid inflammation development and growth. Mechanistically, DDR1 interacted with ARF6, which promoted transport of DDR1 to the plasma membrane and amplified collagen I-induced DDR1 signalling, then facilitated binding of DDR1 to STAT3, leading to STAT3 phosphorylation. The combined inhibition of DDR1 and ARF6 synergistically inhibited the keloid inflammation amplifier.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Collectively, these findings reveal the molecular basis of the activation of NF\u03baB and STAT3 signalling\u00a0via collagen I-DDR1 signalling, and expose the role of the ARF6-DDR1 axis in promoting keloid inflammation development, indicating that DDR1 and ARF6 may serve as innovative therapeutic targets in keloid scars.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/bjd\/ljag105","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:43:56Z","timestamp":1773924236000},"page":"280-292","source":"Crossref","is-referenced-by-count":3,"title":["Collagen I-discoidin domain receptor 1 signalling promotes inflammation development during keloid 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