ArticleCell death & disease2018
Loss of GRHL3 leads to TARC/CCL17-mediated keratinocyte proliferation in the epidermis.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Meta-Analysis ofGenes · 2019Pooled it
- Review
- Loss of the epithelial transcription factor grhl3 leads to variably penetrant developmental phenotypes in zebrafish.Developmental dynamics : an official publication of the American Association of Anatomists · 2025Article
- Glutamine and serum starvation alters the ATP production, oxidative stress, and abundance of mitochondrial RNAs in extracellular vesicles produced by cancer cells.Scientific reports · 2024Article
- Metastatic patterns and treatment options for head and neck cutaneous squamous cell carcinoma (Review).Molecular and clinical oncology · 2024Review
- Identification of a non-canonical chemokine-receptor pathway suppressing regulatory T cells to drive atherosclerosis.Nature cardiovascular research · 2024Article
- Exploration of the Correlation BetweenPharmacogenomics and personalized medicine · 2024Article
- Pro-inflammatory cytokine IL-6 regulates LMO4 expression in psoriatic keratinocytes via AKT/STAT3 pathway.Immunity, inflammation and disease · 2023Article
- Dysregulation of Grainyhead-like 3 expression causes widespread developmental defects.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Article
- YBX1 integration of oncogenic PI3K/mTOR signalling regulates the fitness of malignant epithelial cells.Nature communications · 2023Article
- Grainyhead-like (Grhl) Target Genes in Development and Cancer.International journal of molecular sciences · 2022Review
- Advances in the pathogenesis of psoriasis: from keratinocyte perspective.Cell death & disease · 2022Review
- GRHL2 Expression Functions in Breast Cancer Aggressiveness and Could Serve as Prognostic and Diagnostic Biomarker for Breast Cancer.Clinical Medicine Insights. Oncology · 2022Article
- The Balance between Differentiation and Terminal Differentiation Maintains Oral Epithelial Homeostasis.Cancers · 2021Review
- Grhl3 promotes retention of epidermal cells under endocytic stress to maintain epidermal architecture in zebrafish.PLoS genetics · 2021Article
- The functional GRHL3-filaggrin axis maintains a tumor differentiation potential and influences drug sensitivity.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury.Scientific reports · 2021Article
- Recent Discoveries on the Involvement of Krüppel-Like Factor 4 in the Most Common Cancer Types.International journal of molecular sciences · 2020Review
- Topical Aminosalicylic Acid Improves Keratinocyte Differentiation in an Inducible Mouse Model of Harlequin Ichthyosis.Cell reports. Medicine · 2020Article
- Multi-omics profiling of calcium-induced human keratinocytes differentiation reveals modulation of unfolded protein response signaling pathways.Cell cycle (Georgetown, Tex.) · 2019Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Identifying soluble factors that influence epidermal integrity is critical for the development of preventative and therapeutic strategies for disorders such as ichthyosis, psoriasis, dermatitis and epidermal cancers. The transcription factor Grainyhead-like 3 (GRHL3) is essential for maintaining barrier integrity and preventing development of cutaneous squamous cell carcinoma (SCC); however, how loss of this factor, which in the skin is expressed exclusively within suprabasal epidermal layers triggers proliferation of basal keratinocytes, had thus far remained elusive. Our present study identifies thymus and activation-regulated chemokine (TARC) as a novel soluble chemokine mediator of keratinocyte proliferation following loss of GRHL3. Knockdown of GRHL3 in human keratinocytes showed that of 42 cytokines examined, TARC was the only significantly upregulated chemokine. Mouse skin lacking Grhl3 presented an inflammatory response with hallmarks of TARC activation, including heightened induction of blood clotting, increased infiltration of mast cells and pro-inflammatory T cells, increased expression of the pro-proliferative/pro-inflammatory markers CD3 and pSTAT3, and significantly elevated basal keratinocyte proliferation. Treatment of skin cultures lacking Grhl3 with the broad spectrum anti-inflammatory 5-aminosalicylic acid (5ASA) partially restored epidermal differentiation, indicating that abnormal keratinocyte proliferation/differentiation balance is a key driver of barrier dysfunction following loss of Grhl3, and providing a promising therapeutic avenue in the treatment of GRHL3-mediated epidermal disorders.
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