US EPA

5018522 

Journal Article 

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

Morales-Hernández, A; Nacarino-Palma, A; Moreno-Marín, N; Barrasa, E; Paniagua-Quiñones, B; Catalina-Fernández, I; Alvarez-Barrientos, A; Bustelo, XR; Merino, JM; Fernández-Salguero, PM 

2017 

1 

Stem Cell Research
ISSN: 1873-5061 

25 

December 2017 

61-71 

English 

29107893 

10.1016/j.scr.2017.10.009 

WOS:000418262700012 

https://www.scopus.com/inward/record.uri?eid=2-s2.0-85032258354&doi=10.1016%2fj.scr.2017.10.009&partnerID=40&md5=ee84e9811723e091e668520ba1e29e59
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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.