The Fragile X Mental Retardation Protein protects the lung from xenobiotic stress by facilitating the Integrated Stress Response
The Fragile X Mental Retardation Protein protects the lung from xenobiotic stress by facilitating the Integrated Stress Response
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. We find 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 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.
Basu Deblina Sain、Thimmulappa Rajesh、Guha Arjun、Bhavsar Rital、Chattarji Sumantra、Lingamallu Sai Manoz、Veeranna Chandrakanth、Muddashetty Ravi、Bhattacharya Aditi、Gulami Imtiyaz
Institute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus||Trans Disciplinary UniversityJSS Medical College, JSS Academy of Higher Education & ResearchInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK CampusInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK CampusInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus||Centre for Brain Development and Repair (CBDR), inStem, GKVK Campus||National Centre for Biological Sciences, GKVK CampusInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus||Manipal Academy of Higher EducationJSS Medical College, JSS Academy of Higher Education & ResearchInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK CampusInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus||Centre for Brain Development and Repair (CBDR), inStem, GKVK CampusInstitute for Stem Cell Science and Regenerative Medicine (inStem), GKVK Campus||Trans Disciplinary University
基础医学环境科学理论
Stress ResponseLungIntegrated Stress ResponseFMR1FMRP
Basu Deblina Sain,Thimmulappa Rajesh,Guha Arjun,Bhavsar Rital,Chattarji Sumantra,Lingamallu Sai Manoz,Veeranna Chandrakanth,Muddashetty Ravi,Bhattacharya Aditi,Gulami Imtiyaz.The Fragile X Mental Retardation Protein protects the lung from xenobiotic stress by facilitating the Integrated Stress Response[EB/OL].(2025-03-28)[2025-05-06].https://www.biorxiv.org/content/10.1101/2021.03.16.435743.点此复制
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