TY - JOUR T1 - FMRP protects the lung from xenobiotic stress by facilitating the Integrated Stress Response. JF - J Cell Sci Y1 - 2022 A1 - Basu, Deblina Sain A1 - Bhavsar, Rital A1 - Gulami, Imtiyaz A1 - Chavda, Saraswati A1 - Lingamallu, Sai Manoz A1 - Muddashetty, Ravi A1 - Veeranna, Chandrakanth A1 - Chattarji, Sumantra A1 - Thimmulappa, Rajesh A1 - Bhattacharya, Aditi A1 - Guha, Arjun AB -

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.

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