ArticleMolecular biology of the cell2011
A decisive function of transforming growth factor-β/Smad signaling in tissue morphogenesis and differentiation of human HaCaT keratinocytes.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.
- Meta-analysis of genome-wide association studies identifies three new risk loci for atopic dermatitis.Nature genetics · 2011Pooled it
- RNA-seq analysis of host and viral gene expression highlights interaction between varicella zoster virus and keratinocyte differentiation.PLoS pathogens · 2014Trial
- Targeting TGF-β1/miR-21 Pathway in Keratinocytes Reveals Protective Effects of Silymarin on Imiquimod-Induced Psoriasis Mouse Model.JID innovations : skin science from molecules to population health · 2023Article
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- Melanoma secretion of transforming growth factor-β2 leads to loss of epidermal AMBRA1 threatening epidermal integrity and facilitating tumour ulceration.The British journal of dermatology · 2022Article
- Is Vitamin D Deficiency Related to Increased Cancer Risk in Patients with Type 2 Diabetes Mellitus?International journal of molecular sciences · 2021Review
- Epigenetic regulation of TGF-β-induced EMT by JMJD3/KDM6B histone H3K27 demethylase.Oncogenesis · 2021Article
- The Role of MicroRNAs in Epidermal Barrier.International journal of molecular sciences · 2020Review
- Folding Keratin Gene Clusters during Skin Regional Specification.Developmental cell · 2020Article
- Photoaging Protective Effects ofEvidence-based complementary and alternative medicine : eCAM · 2020Article
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- Innate immune cell-epithelial crosstalk during wound repair.The Journal of clinical investigation · 2019Review
- Cell lineage and communication network inference via optimization for single-cell transcriptomics.Nucleic acids research · 2019Article
- An epithelial organoid model with Langerhans cells for assessing virus-host interactions.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2019Article
- Dysregulated miRNAome and Proteome of PPRV Infected Goat PBMCs Reveal a Coordinated Immune Response.Frontiers in immunology · 2018Article
- HPV16-E2 protein modifies self-renewal and differentiation rate in progenitor cells of human immortalized keratinocytes.Virology journal · 2017Article
- Lymphaticovenous bypass decreases pathologic skin changes in upper extremity breast cancer-related lymphedema.Lymphatic research and biology · 2015Article
- Article
- The Role of TGFβ Signaling in Wound Epithelialization.Advances in wound care · 2014Review
- Expression of USP15, TβR-I and Smad7 in psoriasis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism by which transforming growth factor-β (TGFβ) regulates differentiation in human epidermal keratinocytes is still poorly understood. To assess the role of Smad signaling, we engineered human HaCaT keratinocytes either expressing small interfering RNA against Smads2, 3, and 4 or overexpressing Smad7 and verified impaired Smad signaling as decreased Smad phosphorylation, aberrant nuclear translocation, and altered target gene expression. Besides abrogation of TGFβ-dependent growth inhibition in conventional cultures, epidermal morphogenesis and differentiation in organotypic cultures were disturbed, resulting in altered tissue homeostasis with suprabasal proliferation and hyperplasia upon TGFβ treatment. Neutralizing antibodies against TGFβ, similar to blocking the actions of EGF-receptor or keratinocyte growth factor, caused significant growth reduction of Smad7-overexpressing cells, thereby demonstrating that epithelial hyperplasia was attributed to TGFβ-induced "dermis"-derived growth promoting factors. Furthermore impaired Smad signaling not only blocked the epidermal differentiation process or caused epidermal-to-mesenchymal transition but induced a switch to a complex alternative differentiation program, best characterized as mucous/intestinal-type epithelial differentiation. As the same alternative phenotype evolved from both modes of Smad-pathway interference, and reduction of Smad7-overexpression caused reversion to epidermal differentiation, our data suggest that functional TGFβ/Smad signaling, besides regulating epidermal tissue homeostasis, is not only essential for terminal epidermal differentiation but crucial in programming different epithelial differentiation routes.
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