Epithelial-mesenchymal stem cell transition in a human organ: Lessons from lichen planopilaris
| Autor: | Hisayoshi Imanishi, Sreejith Parameswara Panicker, Jonathan A. Hardman, Marta Bertolini, Jérémy Chéret, Ralf Paus, Christopher M. Ward, Francisco Jimenez, Matthew Harries, Tamás Bíró, N Sepp, Enrique Poblet, David M. Ansell |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
0301 basic medicine Pathology medicine.medical_specialty Epithelial-Mesenchymal Transition ResearchInstitutes_Networks_Beacons/MICRA Peroxisome proliferator-activated receptor Dermatology Biology Biochemistry 030207 dermatology & venereal diseases 03 medical and health sciences 0302 clinical medicine Epidermal growth factor Peroxisomes medicine Humans Epithelial–mesenchymal transition Stem Cell Niche Molecular Biology Cells Cultured Aged chemistry.chemical_classification Pioglitazone integumentary system Keratin-15 Mesenchymal stem cell Lichen Planus Mesenchymal Stem Cells Cell Biology Hair follicle PPAR gamma 030104 developmental biology medicine.anatomical_structure chemistry Manchester Institute for Collaborative Research on Ageing embryonic structures Cancer research Female Signal transduction Wound healing Transforming growth factor |
| Zdroj: | Imanishi, H, Ansell, D, Chéret, J, Harries, M, Bertolini, M, Sepp, N, Bíró, T, Poblet, E, Jimenez, F, Hardman, J, Parameswara Panicker, S, Ward, C & Paus, R 2017, ' Epithelial-mesenchymal stem cell transition in a human organ: Lessons from lichen planopilaris ', Journal of Investigative Dermatology . https://doi.org/10.1016/j.jid.2017.09.047 |
| DOI: | 10.1016/j.jid.2017.09.047 |
| Popis: | Epithelial-to-mesenchymal transition (EMT) is critical for embryonic development and wound healing, and occurs in fibrotic disease and carcinoma. Here, we show that EMT also occurs within the bulge, the epithelial stem cell (eSC) niche of human scalp hair follicles, during the inflammatory permanent alopecia, lichen planopilaris. We show that a molecular EMT signature can be experimentally induced in healthy human eSCs in situ by antagonizing E-cadherin, combined with transforming growth factor-β1, epidermal growth factor, and IFN-γ administration, which to our knowledge has not been reported previously. Moreover, induction of EMT within primary human eSCs can be prevented and even partially reversed ex vivo by peroxisome proliferator-activated receptor-γ agonists, likely through suppression of the transforming growth factor-β signaling pathway. Furthermore, we show that peroxisome proliferator-activated receptor-γ agonists also attenuates the EMT signature even in lesional lichen planopilaris hair follicles ex vivo. We introduce lichen planopilaris as a model disease for pathological EMT in human adult eSCs, report a preclinical assay for therapeutically manipulating eSC EMT within a healthy human (mini-)organ, and show that peroxisome proliferator-activated receptor-γ agonists are promising agents for suppressing and partially reversing EMT in human hair follicles eSCs ex vivo, including in lichen planopilaris. |
| Databáze: | OpenAIRE |
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