Keratinocyte-specific ablation of Stat3 exhibits impaired skin remodeling, but does not affect skin morphogenesis
Open accessAbstract
To elucidate the biological role of Stat3 in the skin, conditional gene targeting using the Cre-loxP system was performed as germline Stat3 ablation leads to embryonic lethality. K5-Cre;Stat3(flox/-) transgenic mice, whose epidermal and follicular keratinocytes lack functional Stat3, were viable and the development of epidermis and hair follicles appeared normal. However, hair cycle and wound healing processes were severely compromised. Furthermore, mutant mice expressed sparse hair and developed spontaneously occurring ulcers with age. Growth factor-dependent in vitro migration of Stat3-disrupted keratinocytes was impaired despite normal proliferative responses. We therefore conclude that Stat3 plays a crucial role in transducing a signal required for migration but not for proliferation of keratinocytes, and that Stat3 is essential for skin remodeling, including hair cycle and wound healing.
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Keratinocyte-specific STAT3 knockout impairs the hair cycle and skin wound healing.
“Impaired hair cycle and skin wound healing”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Sano et al., 1999
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“TheseKOstudies also revealed the role of STAT3 in wound healing of all epithelial cells (Pickert et al., 2009), including cutaneous (Sano et al., 1999) and respiratory epithelium (Hokuto et al., 2004), and its role in lipid metabolism (Cernkovich et al., 2008) and reproduction (Robker et al., 2014).”
BackgroundImpaired Epidermal to Dendritic T Cell Signaling Slows Wound Repair in Aged Skin
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A tissue injury sensing and repair pathway distinct from host pathogen defense
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“Keratinocyte-specific STAT3 knockout in mice leads to impaired skin remodeling that results from impaired epidermal cell regeneration, confirming a central role for STAT3 in normal wound healing.(27) In the gut, STAT3 activation in intestinal epithelial cells regulates immune homeostasis.”
- Authors
- Sano, S., Itami, S., Takeda, K., Tarutani, M., Yamaguchi, Y., Miura, H., Yoshikawa, K., Akira, S., & Takeda, J.
- Affiliations
- The University of Osaka (JP)
- Osaka University Hospital (JP)
- Hyogo Medical University (JP)
- Corresponding author
- Takeda, Junji
- Venue
- The EMBO Journal
- Published
- 1999-09-01
- Volume
- 18
- Issue
- 17
- Pages
- 4657-4668
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1171539
- OpenAlex
- W2043911925
- Cited by
- 519
- References
- 1
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 12 · 2022: 15 · 2021: 16 · 2020: 10 · 2019: 14 · 2018: 17 · 2017: 10 · 2016: 21 · 2015: 20 · 2014: 14 · 2013: 23 · 2012: 23
- FWCI
- 7.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Keywords
- STAT3, keratinocytes, dermal remodeling, skin morphogenesis, hair cycle, wound healing, keratinocyte migration, keratinocyte proliferation, conditional gene targeting, hair follicle, ulcers
- MeSH terms
- Age Factors, Alleles, Animals, Cell Cycle, Cell Movement, DNA-Binding Proteins, Growth Substances, Hair, Mice, Transgenic, Models, Biological, Morphogenesis, Phenotype, Promoter Regions, Genetic, Skin, Time Factors, Viral Proteins, Wound Healing, Trans-Activators, Keratinocytes, Mutagenesis, Gene Targeting, Integrases, STAT3 Transcription Factor, Mice
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