guest ::
| Home > Publications database > Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis. > print |
| Home > Publications database > Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis. > print |
| 001 | 309617 | ||
| 005 | 20260204142438.0 | ||
| 024 | 7 | _ | |a 10.1038/s41392-025-02541-z |2 doi |
| 024 | 7 | _ | |a pmid:41629266 |2 pmid |
| 024 | 7 | _ | |a 2095-9907 |2 ISSN |
| 024 | 7 | _ | |a 2059-3635 |2 ISSN |
| 037 | _ | _ | |a DKFZ-2026-00267 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Li, Li |0 P:(DE-He78)4a1b2b7196b7ebb1cbae04bc115edecc |b 0 |e First author |
| 245 | _ | _ | |a Wnt-associated DKK3 in keratinocytes mediates radiation-induced hyperplasia, dermatitis and skin fibrosis. |
| 260 | _ | _ | |a London |c 2026 |b Macmillan Publishers, part of Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1770211385_2119850 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a #EA:E055#EA:A411#LA:A411#LA:E055# / #NCTZFB26# |
| 520 | _ | _ | |a Radiotherapy 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. |
| 536 | _ | _ | |a 319H - Addenda (POF4-319H) |0 G:(DE-HGF)POF4-319H |c POF4-319H |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de |
| 650 | _ | 7 | |a DKK3 protein, human |2 NLM Chemicals |
| 650 | _ | 7 | |a Dkk3 protein, mouse |2 NLM Chemicals |
| 650 | _ | 7 | |a Adaptor Proteins, Signal Transducing |2 NLM Chemicals |
| 650 | _ | 7 | |a Intercellular Signaling Peptides and Proteins |2 NLM Chemicals |
| 650 | _ | 2 | |a Keratinocytes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Keratinocytes: pathology |2 MeSH |
| 650 | _ | 2 | |a Keratinocytes: radiation effects |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Wnt Signaling Pathway: genetics |2 MeSH |
| 650 | _ | 2 | |a Wnt Signaling Pathway: radiation effects |2 MeSH |
| 650 | _ | 2 | |a Fibrosis: genetics |2 MeSH |
| 650 | _ | 2 | |a Fibrosis: pathology |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Hyperplasia: genetics |2 MeSH |
| 650 | _ | 2 | |a Hyperplasia: pathology |2 MeSH |
| 650 | _ | 2 | |a Hyperplasia: metabolism |2 MeSH |
| 650 | _ | 2 | |a Adaptor Proteins, Signal Transducing: genetics |2 MeSH |
| 650 | _ | 2 | |a Adaptor Proteins, Signal Transducing: metabolism |2 MeSH |
| 650 | _ | 2 | |a Skin: pathology |2 MeSH |
| 650 | _ | 2 | |a Skin: radiation effects |2 MeSH |
| 650 | _ | 2 | |a Skin: metabolism |2 MeSH |
| 650 | _ | 2 | |a Intercellular Signaling Peptides and Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Radiodermatitis: genetics |2 MeSH |
| 650 | _ | 2 | |a Radiodermatitis: pathology |2 MeSH |
| 650 | _ | 2 | |a Radiodermatitis: metabolism |2 MeSH |
| 700 | 1 | _ | |a Lopez Perez, Ramon |0 P:(DE-He78)c5a1a98649a7874de0def093eb136262 |b 1 |u dkfz |
| 700 | 1 | _ | |a Shehzad, Khuram |b 2 |
| 700 | 1 | _ | |a Jennemann, Richard |0 P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d |b 3 |u dkfz |
| 700 | 1 | _ | |a Schmidt, Claudia |0 P:(DE-He78)2a599a43bd0b5910c80edb288d8da3e5 |b 4 |u dkfz |
| 700 | 1 | _ | |a Walle, Thomas |0 P:(DE-He78)51635089578f68fc9efdb61e6a760b64 |b 5 |u dkfz |
| 700 | 1 | _ | |a Tietz-Dahlfuß, Alexandra |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Grimm, Elisabeth |0 P:(DE-He78)e5f0e1cbcf3bdcd6a95dcd0fe056f704 |b 7 |u dkfz |
| 700 | 1 | _ | |a Kraske, Joscha |0 P:(DE-He78)7fb0841f5e88928308e29474e3170818 |b 8 |u dkfz |
| 700 | 1 | _ | |a Häring, Peter |0 P:(DE-HGF)0 |b 9 |
| 700 | 1 | _ | |a Barayeu, Uladzimir |0 P:(DE-He78)387d4f13f0c0f8a92fee635038e7d424 |b 10 |
| 700 | 1 | _ | |a Dick, Tobias P |0 P:(DE-He78)7f55a0ed8b021080de00960cc73768fb |b 11 |u dkfz |
| 700 | 1 | _ | |a Ye, Luxi |0 P:(DE-He78)96e7b84613a9b63b293faa3951427167 |b 12 |
| 700 | 1 | _ | |a Braun, Stephan A |b 13 |
| 700 | 1 | _ | |a Hertl, Michael |b 14 |
| 700 | 1 | _ | |a Worzfeld, Thomas |b 15 |
| 700 | 1 | _ | |a Wiech, Thorsten |b 16 |
| 700 | 1 | _ | |a Ji, Huihui |b 17 |
| 700 | 1 | _ | |a Su, Jing |b 18 |
| 700 | 1 | _ | |a Schneeweiss, Jonathan M |b 19 |
| 700 | 1 | _ | |a Liu, Muzi |0 P:(DE-He78)adccfec91f7014790171d2fe4d540131 |b 20 |u dkfz |
| 700 | 1 | _ | |a Kommoss, Katharina |0 P:(DE-He78)47a1ded1dddd8c84bd3a6e3f6e1e8769 |b 21 |u dkfz |
| 700 | 1 | _ | |a Heikenwälder, Matthias |0 P:(DE-HGF)0 |b 22 |
| 700 | 1 | _ | |a Zou, Bingwen |b 23 |
| 700 | 1 | _ | |a Mücklich, Sabrina |b 24 |
| 700 | 1 | _ | |a Steinbrink, Kerstin |b 25 |
| 700 | 1 | _ | |a Raker, Verena K |0 0000-0001-7264-0371 |b 26 |
| 700 | 1 | _ | |a Wu, Wenjun |0 P:(DE-He78)c9c21d72fdb58bb5185bb56e26e62899 |b 27 |
| 700 | 1 | _ | |a Noessner, Elfriede |b 28 |
| 700 | 1 | _ | |a Gröne, Hermann-Josef |b 29 |
| 700 | 1 | _ | |a Nelson, Peter J |b 30 |
| 700 | 1 | _ | |a Sandhoff, Roger |0 P:(DE-He78)a928ded2085c8911822370cad0b4a728 |b 31 |e Last author |u dkfz |
| 700 | 1 | _ | |a Huber, Peter |0 P:(DE-He78)3291aaac20f3d603d96744c1f0890028 |b 32 |e Last author |u dkfz |
| 773 | _ | _ | |a 10.1038/s41392-025-02541-z |g Vol. 11, no. 1, p. 41 |0 PERI:(DE-600)2886872-9 |n 1 |p 41 |t Signal transduction and targeted therapy |v 11 |y 2026 |x 2095-9907 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:309617 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 0 |6 P:(DE-He78)4a1b2b7196b7ebb1cbae04bc115edecc |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 1 |6 P:(DE-He78)c5a1a98649a7874de0def093eb136262 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 3 |6 P:(DE-He78)3caae9893e3b2704f7bb5a9646ef084d |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 4 |6 P:(DE-He78)2a599a43bd0b5910c80edb288d8da3e5 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 5 |6 P:(DE-He78)51635089578f68fc9efdb61e6a760b64 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 6 |6 P:(DE-HGF)0 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 7 |6 P:(DE-He78)e5f0e1cbcf3bdcd6a95dcd0fe056f704 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 8 |6 P:(DE-He78)7fb0841f5e88928308e29474e3170818 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 9 |6 P:(DE-HGF)0 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 10 |6 P:(DE-He78)387d4f13f0c0f8a92fee635038e7d424 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 11 |6 P:(DE-He78)7f55a0ed8b021080de00960cc73768fb |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 12 |6 P:(DE-He78)96e7b84613a9b63b293faa3951427167 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 20 |6 P:(DE-He78)adccfec91f7014790171d2fe4d540131 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 21 |6 P:(DE-He78)47a1ded1dddd8c84bd3a6e3f6e1e8769 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 22 |6 P:(DE-HGF)0 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 27 |6 P:(DE-He78)c9c21d72fdb58bb5185bb56e26e62899 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 31 |6 P:(DE-He78)a928ded2085c8911822370cad0b4a728 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 32 |6 P:(DE-He78)3291aaac20f3d603d96744c1f0890028 |
| 913 | 1 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF4-310 |0 G:(DE-HGF)POF4-319H |3 G:(DE-HGF)POF4 |2 G:(DE-HGF)POF4-300 |4 G:(DE-HGF)POF |v Addenda |x 0 |
| 914 | 1 | _ | |y 2026 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0200 |2 StatID |b SCOPUS |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0300 |2 StatID |b Medline |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0501 |2 StatID |b DOAJ Seal |d 2024-04-10T15:44:53Z |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0500 |2 StatID |b DOAJ |d 2024-04-10T15:44:53Z |
| 915 | _ | _ | |a Peer Review |0 StatID:(DE-HGF)0030 |2 StatID |b DOAJ : Anonymous peer review |d 2024-04-10T15:44:53Z |
| 915 | _ | _ | |a Creative Commons Attribution CC BY (No Version) |0 LIC:(DE-HGF)CCBYNV |2 V:(DE-HGF) |b DOAJ |d 2024-04-10T15:44:53Z |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0199 |2 StatID |b Clarivate Analytics Master Journal List |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1050 |2 StatID |b BIOSIS Previews |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0160 |2 StatID |b Essential Science Indicators |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)1190 |2 StatID |b Biological Abstracts |d 2024-12-17 |
| 915 | _ | _ | |a WoS |0 StatID:(DE-HGF)0113 |2 StatID |b Science Citation Index Expanded |d 2024-12-17 |
| 915 | _ | _ | |a DBCoverage |0 StatID:(DE-HGF)0150 |2 StatID |b Web of Science Core Collection |d 2024-12-17 |
| 915 | _ | _ | |a JCR |0 StatID:(DE-HGF)0100 |2 StatID |b SIGNAL TRANSDUCT TAR : 2022 |d 2024-12-17 |
| 915 | _ | _ | |a IF >= 30 |0 StatID:(DE-HGF)9930 |2 StatID |b SIGNAL TRANSDUCT TAR : 2022 |d 2024-12-17 |
| 915 | _ | _ | |a Article Processing Charges |0 StatID:(DE-HGF)0561 |2 StatID |d 2024-12-17 |
| 915 | _ | _ | |a Fees |0 StatID:(DE-HGF)0700 |2 StatID |d 2024-12-17 |
| 920 | 2 | _ | |0 I:(DE-He78)A411-20160331 |k A411 |l Lipid-Pathobiochemie |x 0 |
| 920 | 2 | _ | |0 I:(DE-He78)E055-20160331 |k E055 |l E055 KKE Molekulare Radioonkologie |x 1 |
| 920 | 1 | _ | |0 I:(DE-He78)E055-20160331 |k E055 |l E055 KKE Molekulare Radioonkologie |x 0 |
| 920 | 1 | _ | |0 I:(DE-He78)A411-20160331 |k A411 |l Lipid-Pathobiochemie |x 1 |
| 920 | 1 | _ | |0 I:(DE-He78)W250-20160331 |k W250 |l Präklinische und Translationale Pathologie Core Facility |x 2 |
| 920 | 1 | _ | |0 I:(DE-He78)E040-20160331 |k E040 |l E040 Med. Physik in der Strahlentherapie |x 3 |
| 920 | 1 | _ | |0 I:(DE-He78)A160-20160331 |k A160 |l A160 Redoxregulation |x 4 |
| 920 | 1 | _ | |0 I:(DE-He78)D440-20160331 |k D440 |l Chronische Entzündung und Krebs |x 5 |
| 920 | 1 | _ | |0 I:(DE-He78)HD02-20160331 |k HD02 |l Koordinierungsstelle NCT Heidelberg |x 6 |
| 920 | 0 | _ | |0 I:(DE-He78)E055-20160331 |k E055 |l E055 KKE Molekulare Radioonkologie |x 0 |
| 920 | 0 | _ | |0 I:(DE-He78)A411-20160331 |k A411 |l Lipid-Pathobiochemie |x 1 |
| 980 | _ | _ | |a journal |
| 980 | _ | _ | |a VDB |
| 980 | _ | _ | |a I:(DE-He78)E055-20160331 |
| 980 | _ | _ | |a I:(DE-He78)A411-20160331 |
| 980 | _ | _ | |a I:(DE-He78)W250-20160331 |
| 980 | _ | _ | |a I:(DE-He78)E040-20160331 |
| 980 | _ | _ | |a I:(DE-He78)A160-20160331 |
| 980 | _ | _ | |a I:(DE-He78)D440-20160331 |
| 980 | _ | _ | |a I:(DE-He78)HD02-20160331 |
| 980 | _ | _ | |a UNRESTRICTED |
| Library | Collection | CLSMajor | CLSMinor | Language | Author |
|---|