000309617 001__ 309617
000309617 005__ 20260204142438.0
000309617 0247_ $$2doi$$a10.1038/s41392-025-02541-z
000309617 0247_ $$2pmid$$apmid:41629266
000309617 0247_ $$2ISSN$$a2095-9907
000309617 0247_ $$2ISSN$$a2059-3635
000309617 037__ $$aDKFZ-2026-00267
000309617 041__ $$aEnglish
000309617 082__ $$a610
000309617 1001_ $$0P:(DE-He78)4a1b2b7196b7ebb1cbae04bc115edecc$$aLi, Li$$b0$$eFirst author
000309617 245__ $$aWnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis.
000309617 260__ $$aLondon$$bMacmillan Publishers, part of Springer Nature$$c2026
000309617 3367_ $$2DRIVER$$aarticle
000309617 3367_ $$2DataCite$$aOutput Types/Journal article
000309617 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1770211385_2119850
000309617 3367_ $$2BibTeX$$aARTICLE
000309617 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000309617 3367_ $$00$$2EndNote$$aJournal Article
000309617 500__ $$a#EA:E055#EA:A411#LA:A411#LA:E055# / #NCTZFB26#
000309617 520__ $$aRadiotherapy remains a mainstay of cancer treatment. However, radiotherapy can also elicit acute and chronic adverse effects, including dermal inflammation and skin fibrosis. A comprehensive understanding of the underlying fibrotic processes remains elusive, and currently, no established treatment options exist. Canonical Wnt signaling has emerged as a significant player in fibrotic conditions. The Dickkopf (DKK) protein family comprises key modulators of Wnt signaling. To define the function of DKK3 in radiation-induced skin damage, we combined complementary in vivo and in vitro approaches, including a 3D human skin model, mice with cell-type-specific Dkk3 deletions, and irradiated human skin specimens. Our study revealed the pivotal role of DKK3 in regulating the response of the skin to radiation, with diminished DKK3 significantly mitigating radiation-induced skin damage. We found that radiation increases DKK3 expression in basal keratinocytes, leading to elevated ROS levels, TGF-β-mediated Wnt activation, epidermal hyperplasia, and subsequent skin fibrosis. Increased keratinocyte expression of DKK3 also drives macrophage polarization toward a CD163highCD206high profibrotic M2 phenotype, activating myofibroblasts and leading to fibrosis. Notably, DKK3 deficiency in keratinocytes markedly reduces radiation-induced dermal hyperplasia and fibrosis, identifying DKK3 as a key regulator of cutaneous radiation responses. These findings position DKK3 as a promising upstream modulator of TGF-β signaling for mitigating radiation-induced dermatitis and fibrosis, with potential relevance to other fibrotic diseases.
000309617 536__ $$0G:(DE-HGF)POF4-319H$$a319H - Addenda (POF4-319H)$$cPOF4-319H$$fPOF IV$$x0
000309617 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000309617 650_7 $$2NLM Chemicals$$aDKK3 protein, human
000309617 650_7 $$2NLM Chemicals$$aDkk3 protein, mouse
000309617 650_7 $$2NLM Chemicals$$aAdaptor Proteins, Signal Transducing
000309617 650_7 $$2NLM Chemicals$$aIntercellular Signaling Peptides and Proteins
000309617 650_2 $$2MeSH$$aKeratinocytes: metabolism
000309617 650_2 $$2MeSH$$aKeratinocytes: pathology
000309617 650_2 $$2MeSH$$aKeratinocytes: radiation effects
000309617 650_2 $$2MeSH$$aAnimals
000309617 650_2 $$2MeSH$$aHumans
000309617 650_2 $$2MeSH$$aWnt Signaling Pathway: genetics
000309617 650_2 $$2MeSH$$aWnt Signaling Pathway: radiation effects
000309617 650_2 $$2MeSH$$aFibrosis: genetics
000309617 650_2 $$2MeSH$$aFibrosis: pathology
000309617 650_2 $$2MeSH$$aMice
000309617 650_2 $$2MeSH$$aHyperplasia: genetics
000309617 650_2 $$2MeSH$$aHyperplasia: pathology
000309617 650_2 $$2MeSH$$aHyperplasia: metabolism
000309617 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: genetics
000309617 650_2 $$2MeSH$$aAdaptor Proteins, Signal Transducing: metabolism
000309617 650_2 $$2MeSH$$aSkin: pathology
000309617 650_2 $$2MeSH$$aSkin: radiation effects
000309617 650_2 $$2MeSH$$aSkin: metabolism
000309617 650_2 $$2MeSH$$aIntercellular Signaling Peptides and Proteins: genetics
000309617 650_2 $$2MeSH$$aRadiodermatitis: genetics
000309617 650_2 $$2MeSH$$aRadiodermatitis: pathology
000309617 650_2 $$2MeSH$$aRadiodermatitis: metabolism
000309617 7001_ $$0P:(DE-He78)c5a1a98649a7874de0def093eb136262$$aLopez Perez, Ramon$$b1$$udkfz
000309617 7001_ $$aShehzad, Khuram$$b2
000309617 7001_ $$0P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d$$aJennemann, Richard$$b3$$udkfz
000309617 7001_ $$0P:(DE-He78)2a599a43bd0b5910c80edb288d8da3e5$$aSchmidt, Claudia$$b4$$udkfz
000309617 7001_ $$0P:(DE-He78)51635089578f68fc9efdb61e6a760b64$$aWalle, Thomas$$b5$$udkfz
000309617 7001_ $$0P:(DE-HGF)0$$aTietz-Dahlfuß, Alexandra$$b6
000309617 7001_ $$0P:(DE-He78)e5f0e1cbcf3bdcd6a95dcd0fe056f704$$aGrimm, Elisabeth$$b7$$udkfz
000309617 7001_ $$0P:(DE-He78)7fb0841f5e88928308e29474e3170818$$aKraske, Joscha$$b8$$udkfz
000309617 7001_ $$0P:(DE-HGF)0$$aHäring, Peter$$b9
000309617 7001_ $$0P:(DE-He78)387d4f13f0c0f8a92fee635038e7d424$$aBarayeu, Uladzimir$$b10
000309617 7001_ $$0P:(DE-He78)7f55a0ed8b021080de00960cc73768fb$$aDick, Tobias P$$b11$$udkfz
000309617 7001_ $$0P:(DE-He78)96e7b84613a9b63b293faa3951427167$$aYe, Luxi$$b12
000309617 7001_ $$aBraun, Stephan A$$b13
000309617 7001_ $$aHertl, Michael$$b14
000309617 7001_ $$aWorzfeld, Thomas$$b15
000309617 7001_ $$aWiech, Thorsten$$b16
000309617 7001_ $$aJi, Huihui$$b17
000309617 7001_ $$aSu, Jing$$b18
000309617 7001_ $$aSchneeweiss, Jonathan M$$b19
000309617 7001_ $$0P:(DE-He78)adccfec91f7014790171d2fe4d540131$$aLiu, Muzi$$b20$$udkfz
000309617 7001_ $$0P:(DE-He78)47a1ded1dddd8c84bd3a6e3f6e1e8769$$aKommoss, Katharina$$b21$$udkfz
000309617 7001_ $$0P:(DE-HGF)0$$aHeikenwälder, Matthias$$b22
000309617 7001_ $$aZou, Bingwen$$b23
000309617 7001_ $$aMücklich, Sabrina$$b24
000309617 7001_ $$aSteinbrink, Kerstin$$b25
000309617 7001_ $$00000-0001-7264-0371$$aRaker, Verena K$$b26
000309617 7001_ $$0P:(DE-He78)c9c21d72fdb58bb5185bb56e26e62899$$aWu, Wenjun$$b27
000309617 7001_ $$aNoessner, Elfriede$$b28
000309617 7001_ $$aGröne, Hermann-Josef$$b29
000309617 7001_ $$aNelson, Peter J$$b30
000309617 7001_ $$0P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aSandhoff, Roger$$b31$$eLast author$$udkfz
000309617 7001_ $$0P:(DE-He78)3291aaac20f3d603d96744c1f0890028$$aHuber, Peter$$b32$$eLast author$$udkfz
000309617 773__ $$0PERI:(DE-600)2886872-9$$a10.1038/s41392-025-02541-z$$gVol. 11, no. 1, p. 41$$n1$$p41$$tSignal transduction and targeted therapy$$v11$$x2095-9907$$y2026
000309617 909CO $$ooai:inrepo02.dkfz.de:309617$$pVDB
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)4a1b2b7196b7ebb1cbae04bc115edecc$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c5a1a98649a7874de0def093eb136262$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d$$aDeutsches Krebsforschungszentrum$$b3$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2a599a43bd0b5910c80edb288d8da3e5$$aDeutsches Krebsforschungszentrum$$b4$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)51635089578f68fc9efdb61e6a760b64$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b6$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)e5f0e1cbcf3bdcd6a95dcd0fe056f704$$aDeutsches Krebsforschungszentrum$$b7$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7fb0841f5e88928308e29474e3170818$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b9$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)387d4f13f0c0f8a92fee635038e7d424$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7f55a0ed8b021080de00960cc73768fb$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)96e7b84613a9b63b293faa3951427167$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)adccfec91f7014790171d2fe4d540131$$aDeutsches Krebsforschungszentrum$$b20$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)47a1ded1dddd8c84bd3a6e3f6e1e8769$$aDeutsches Krebsforschungszentrum$$b21$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-HGF)0$$aDeutsches Krebsforschungszentrum$$b22$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c9c21d72fdb58bb5185bb56e26e62899$$aDeutsches Krebsforschungszentrum$$b27$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a928ded2085c8911822370cad0b4a728$$aDeutsches Krebsforschungszentrum$$b31$$kDKFZ
000309617 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)3291aaac20f3d603d96744c1f0890028$$aDeutsches Krebsforschungszentrum$$b32$$kDKFZ
000309617 9131_ $$0G:(DE-HGF)POF4-319H$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vAddenda$$x0
000309617 9141_ $$y2026
000309617 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0501$$2StatID$$aDBCoverage$$bDOAJ Seal$$d2024-04-10T15:44:53Z
000309617 915__ $$0StatID:(DE-HGF)0500$$2StatID$$aDBCoverage$$bDOAJ$$d2024-04-10T15:44:53Z
000309617 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bDOAJ : Anonymous peer review$$d2024-04-10T15:44:53Z
000309617 915__ $$0LIC:(DE-HGF)CCBYNV$$2V:(DE-HGF)$$aCreative Commons Attribution CC BY (No Version)$$bDOAJ$$d2024-04-10T15:44:53Z
000309617 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bSIGNAL TRANSDUCT TAR : 2022$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)9930$$2StatID$$aIF >= 30$$bSIGNAL TRANSDUCT TAR : 2022$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0561$$2StatID$$aArticle Processing Charges$$d2024-12-17
000309617 915__ $$0StatID:(DE-HGF)0700$$2StatID$$aFees$$d2024-12-17
000309617 9202_ $$0I:(DE-He78)A411-20160331$$kA411$$lLipid-Pathobiochemie$$x0
000309617 9202_ $$0I:(DE-He78)E055-20160331$$kE055$$lE055 KKE Molekulare Radioonkologie$$x1
000309617 9201_ $$0I:(DE-He78)E055-20160331$$kE055$$lE055 KKE Molekulare Radioonkologie$$x0
000309617 9201_ $$0I:(DE-He78)A411-20160331$$kA411$$lLipid-Pathobiochemie$$x1
000309617 9201_ $$0I:(DE-He78)W250-20160331$$kW250$$lPräklinische und Translationale Pathologie Core Facility$$x2
000309617 9201_ $$0I:(DE-He78)E040-20160331$$kE040$$lE040 Med. Physik in der Strahlentherapie$$x3
000309617 9201_ $$0I:(DE-He78)A160-20160331$$kA160$$lA160 Redoxregulation$$x4
000309617 9201_ $$0I:(DE-He78)D440-20160331$$kD440$$lChronische Entzündung und Krebs$$x5
000309617 9201_ $$0I:(DE-He78)HD02-20160331$$kHD02$$lKoordinierungsstelle NCT Heidelberg$$x6
000309617 9200_ $$0I:(DE-He78)E055-20160331$$kE055$$lE055 KKE Molekulare Radioonkologie$$x0
000309617 9200_ $$0I:(DE-He78)A411-20160331$$kA411$$lLipid-Pathobiochemie$$x1
000309617 980__ $$ajournal
000309617 980__ $$aVDB
000309617 980__ $$aI:(DE-He78)E055-20160331
000309617 980__ $$aI:(DE-He78)A411-20160331
000309617 980__ $$aI:(DE-He78)W250-20160331
000309617 980__ $$aI:(DE-He78)E040-20160331
000309617 980__ $$aI:(DE-He78)A160-20160331
000309617 980__ $$aI:(DE-He78)D440-20160331
000309617 980__ $$aI:(DE-He78)HD02-20160331
000309617 980__ $$aUNRESTRICTED