Epithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation

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dc.contributor.authorHoste, Esther
dc.contributor.authorMaueroder, Christian
dc.contributor.authorvan Hove, Lisette
dc.contributor.authorCatrysse, Leen
dc.contributor.authorVikkula, Hanna-Kaisa
dc.contributor.authorSze, Mozes
dc.contributor.authorMaes, Bastiaan
dc.contributor.authorKarjosukarso, Dyah
dc.contributor.authorMartens, Liesbet
dc.contributor.authorGoncalves, Amanda
dc.contributor.authorParthoens, Eef
dc.contributor.authorRoelandt, Ria
dc.contributor.authorDeclercq, Wim
dc.contributor.authorFuentes, Ignacia
dc.contributor.authorPalisson, Francis
dc.contributor.authorGonzalez, Sergio
dc.contributor.authorSalas-Alanis, Julio C.
dc.contributor.authorBoon, Louis
dc.contributor.authorHuebener, Peter
dc.contributor.authorMulder, Klaas Willem
dc.contributor.authorRavichandran, Kodi
dc.contributor.authorSaeys, Yvan
dc.contributor.authorSchwabe, Robert Felix
dc.contributor.authorvan Loo, Geert
dc.date.accessioned2025-01-23T21:09:32Z
dc.date.available2025-01-23T21:09:32Z
dc.date.issued2019
dc.description.abstractRegenerative responses predispose tissues to tumor formation by largely unknown mechanisms. High-mobility group box 1 (HMGB1) is a danger-associated molecular pattern contributing to inflammatory pathologies. We show that HMGB1 derived from keratinocytes, but not myeloid cells, delays cutaneous wound healing and drives tumor formation. In wounds of mice lacking HMGB1 selectively in keratinocytes, a marked reduction in neutrophil extracellular trap (NET) formation is observed. Pharmacological targeting of HMGB1 or NETs prevents skin tumorigenesis and accelerates wound regeneration. HMGB1-dependent NET formation and skin tumorigenesis is orchestrated by tumor necrosis factor (TNF) and requires RIPK1 kinase activity. NETs are present in the microenvironment of keratinocyte-derived tumors in mice and lesional and tumor skin of patients suffering from recessive dystrophic epidermolysis bullosa, a disease in which skin blistering predisposes to tumorigenesis. We conclude that tumorigenicity of the wound microenvironment depends on epithelial-derived HMGB1 regulating NET formation, thereby establishing a mechanism linking reparative inflammation to tumor initiation.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.celrep.2019.10.104
dc.identifier.issn2211-1247
dc.identifier.urihttps://doi.org/10.1016/j.celrep.2019.10.104
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/100820
dc.identifier.wosidWOS:000499377000014
dc.issue.numero9
dc.language.isoen
dc.pagina.final2701
dc.pagina.inicio2689
dc.revistaCell reports
dc.rightsacceso restringido
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleEpithelial HMGB1 Delays Skin Wound Healing and Drives Tumor Initiation by Priming Neutrophils for NET Formation
dc.typeartículo
dc.volumen29
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
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