Lung regeneration after toxic injury is improved in absence of dioxin receptor

Autor: Antonio Morales-Hernández, Ana Nacarino-Palma, Nuria Moreno-Marín, Eva Barrasa, Beroé Paniagua-Quiñones, Inmaculada Catalina-Fernández, Alberto Alvarez-Barrientos, Xosé R. Bustelo, Jaime M. Merino, Pedro M. Fernández-Salguero
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Zdroj: Stem Cell Research, Vol 25, Iss C, Pp 61-71 (2017)
Druh dokumentu: article
ISSN: 1873-5061
1876-7753
DOI: 10.1016/j.scr.2017.10.009
Popis: Recent experimental evidences from cellular systems and from mammalian and non-mammalian animal models highlight novel functions for the aryl hydrocarbon/dioxin receptor (AhR) in maintaining cell differentiation and tissue homeostasis. Notably, AhR depletion stimulates an undifferentiated and pluripotent phenotype likely associated to a mesenchymal transition in epithelial cells and to increased primary tumorigenesis and metastasis in melanoma. In this work, we have used a lung model of epithelial regeneration to investigate whether AhR regulates proper tissue repair by adjusting the expansion of undifferentiated stem-like cells. AhR-null mice developed a faster and more efficient repair of the lung bronchiolar epithelium upon naphthalene injury that required increased cell proliferation and the earlier activation of stem-like Clara, Basal and neuroepithelial cells precursors. Increased basal content in multipotent Sca1+/CD31−/CD4− cells and in cells expressing pluripotency factors NANOG and OCT4 could also improve re-epithelialization in AhR-null lungs. The reduced response of AhR-deficient lungs to Sonic Hedgehog (Shh) repression shortly after injury may also help their improved bronchiolar epithelium repair. These results support a role for AhR in the regenerative response against toxins, and open the possibility of modulating its activation level to favor recovery from lesions caused by environmental contaminants.
Databáze: Directory of Open Access Journals
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