TitleFMRP protects the lung from xenobiotic stress by facilitating the Integrated Stress Response.
Publication TypeJournal Article
Year of Publication2022
AuthorsBasu DSain, Bhavsar R, Gulami I, Chavda S, Lingamallu SManoz, Muddashetty R, Veeranna C, Chattarji S, Thimmulappa R, Bhattacharya A, Guha A
JournalJ Cell Sci
Date Published2022 Mar 23
ISSN1477-9137
Abstract

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 (Nap) 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 FMRP-deficient BEAS-2B 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.

DOI10.1242/jcs.258652
Alternate JournalJ Cell Sci
PubMed ID35319067
Grant ListinStem Core Grant / / Department of Biotechnology /

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