ArticleThe Journal of investigative dermatology2014
Wnt5a/β-catenin signaling drives calcium-induced differentiation of human primary keratinocytes.
Article in The Journal of investigative dermatology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 42 citations in OpenAlex.
- Spondin-1 Inhibits Odontoblastic Differentiation of Human Dental Pulp Stem Cells.Biomolecules · 2026Article
- Spatiotemporal dynamics of mammalian wound healing.Cell discovery · 2026Review
- Mechanistic Insights and Therapeutic Potential of Wnt5a Signaling in Alveolar Epithelial Cell Development and Bronchopulmonary Dysplasia.Stem cell reviews and reports · 2025Review
- Comprehensive secretome profiling and CRISPR screen identifies SFRP1 as a key inhibitor of epidermal progenitor proliferation.Cell death & disease · 2025Article
- Various Cellular Components and Its Signaling Cascades Through the Involvement of Signaling Messengers in Keratinocyte Differentiation.Antioxidants (Basel, Switzerland) · 2025Review
- A Comprehensive Review of Electrolyte Imbalances and Their Applied Aspects in Dermatology.Cureus · 2025Review
- Severe Hypocalcemia as an Unexpected Trigger for Psoriasis Exacerbation in Chronic Hypoparathyroidism: A Case Report.Clinical medicine insights. Case reports · 2025Article
- Convergence of Calcium Channel Regulation and Mechanotransduction in Skeletal Regenerative Biomaterial Design.Advanced healthcare materials · 2023Review
- Protective effect ofFrontiers in pharmacology · 2023Article
- Approaches for Regenerative Healing of Cutaneous Wound with an Emphasis on Strategies Activating the Wnt/β-Catenin Pathway.Advances in wound care · 2022Article
- A Beginner's Introduction to Skin Stem Cells and Wound Healing.International journal of molecular sciences · 2021Review
- A pustular psoriasis flare treated with calcium supplementation.JAAD case reports · 2021Article
- C3a and Its Receptor C3aR Are Detectable in Normal Human Epidermal Keratinocytes and Are Differentially Regulated via TLR3 and LL37.Journal of innate immunity · 2021Article
- Calcium-Sensing Receptor Participates in High Glucose-Induced EndMT in Primary Human Aortic Endothelial Cells.Frontiers in physiology · 2020Article
- Insight Into the Function of RIPK4 in Keratinocyte Differentiation and Carcinogenesis.Frontiers in oncology · 2020Review
- Abnormal keratinocyte differentiation in the nasal planum of Labrador Retrievers with hereditary nasal parakeratosis (HNPK).PloS one · 2020Article
- Fucoidan fromMarine drugs · 2019Article
- The pathological role of Wnt5a in psoriasis and psoriatic arthritis.Journal of cellular and molecular medicine · 2019Review
- Lack of plakoglobin impairs integrity and wound healing in corneal epithelium in mice.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- Intracellular Calcium Determines the Adipogenic Differentiation Potential of Human Umbilical Cord Blood-Derived Mesenchymal Stem Cells via the Wnt5a/Stem cells international · 2018Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
It is well established that a gradient of extracellular calcium within the epidermis regulates the differentiation of keratinocytes. However, the molecular mechanisms implicated in this process are not fully understood. RNA interference of the calcium-sensing receptor (CaSR) showed that CaSR is essential in calcium-induced differentiation of normal human epidermal keratinocytes (NHEKs) by increasing the levels of free intracellular calcium, which upregulates the expression of Wnt5a but not Wnt3a, Wnt4, and Dkk-1 in the cells. Subsequently, autocrine Wnt5a promotes the differentiation of NHEKs, determined by increased biosynthesis of keratin-1 and loricrin, whereas proliferation is suppressed. Addition of both Wnt5a and calcium to NHEKs activated the Wnt/β-catenin signaling pathway as indicated by (i) increased stability of β-catenin in the cells, (ii) enhanced β-catenin transcriptional activity, demonstrated by a luciferase-based β-catenin-activated reporter assay, and (iii) augmented Wnt/β-catenin target gene expression. NHEKs depleted for β-catenin had a significantly reduced susceptibility to calcium-induced differentiation. Knockdown of axin 2, an antagonist of β-catenin stability, enhanced the biosynthesis of keratin-1 and loricrin in the cells. Our findings establish a directional crosstalk between CaSR and Wnt/β-catenin signaling in keratinocyte differentiation via Wnt5a that acts as an autocrine stimulus in this process.
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