FMRP protects the lung from xenobiotic stress by facilitating the integrated stress response.

Autor:	Sain Basu D; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.; Trans Disciplinary University, Yelahanka, Bangalore 560064, India., Bhavsar R; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India., Gulami I; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.; Trans Disciplinary University, Yelahanka, Bangalore 560064, India., Chavda S; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India., Lingamallu SM; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.; Manipal Academy of Higher Education, Madhav Nagar, Manipal 576104, India., Muddashetty R; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India., Veeranna C; Department of Forensic Medicine, JSS Medical College, Mysore 570015, India., Chattarji S; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.; Brain Development and Disease Mechanisms (BDDM), inStem, GKVK Campus, Bangalore 560065, India.; National Centre for Biological Sciences, GKVK Campus, Bangalore 560065, India., Thimmulappa R; JSS Medical College, JSS Academy of Higher Education & Research, Mysore 570015, India., Bhattacharya A; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.; Brain Development and Disease Mechanisms (BDDM), inStem, GKVK Campus, Bangalore 560065, India., Guha A; Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus, Bangalore 560065, India.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2022 May 01; Vol. 135 (9). Date of Electronic Publication: 2022 May 10.
DOI:	10.1242/jcs.258652
Abstrakt:	Stress response pathways protect the lung from the damaging effects of environmental toxicants. Here we investigate the role of the fragile X mental retardation protein (FMRP), a multifunctional protein implicated in stress responses, in the lung. We report that FMRP is expressed in murine and human lungs, in the airways and more broadly. Analysis of airway stress responses in mice and in a murine cell line ex vivo, using the well-established naphthalene injury model, reveals that FMRP-deficient cells exhibit increased expression of markers of oxidative and genotoxic stress and increased cell death. Further inquiry shows that FMRP-deficient cells fail to actuate the integrated stress response pathway (ISR) and upregulate the transcription factor ATF4. Knockdown of ATF4 expression phenocopies the loss of FMRP. We extend our analysis of the role of FMRP to human bronchial BEAS-2B cells, using a 9,10-phenanthrenequinone air pollutant model, to find that FMRP-deficient BEAS-2B cells also fail to actuate the ISR and exhibit greater susceptibility. Taken together, our data suggest that FMRP has a conserved role in protecting the airways by facilitating the ISR. This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interests The authors declare no competing or financial interests. (© 2022. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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