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Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion. This is exacerbated by the fact that almost 60% of PLWH smoke tobacco, which can exacerbate inflammation and mucociliary clearance (MCC) dysfunction. This study shows that HIV Tat alters the microRNAome in airway epithelial cells and upregulates miR-34a-5p with consequent suppression of its target, Sirtuin 1 (SIRT1). SIRT1 is known to suppress Metalloproteinase 17 (ADAM17), a protease activating Notch signaling. HIV and cigarette smoke (CS) upregulate ADAM17. ADAM17 upregulation followed by SIRT1 suppression can lead to decreased ciliation, mucus hypersecretion, and attenuated MCC, a hallmark of chronic bronchitis in smokers and COPD. It is, therefore, essential to understand the pathophysiological mechanism resulting in acquired Notch dysregulation and its downstream impact on HIV-infected smokers.<\/jats:p>","DOI":"10.3390\/cells13232009","type":"journal-article","created":{"date-parts":[[2024,12,5]],"date-time":"2024-12-05T04:13:03Z","timestamp":1733371983000},"page":"2009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["HIV-1 Tat Protein and Cigarette Smoke Mediated ADAM17 Upregulation Can Lead to Impaired Mucociliary Clearance"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6533-6574","authenticated-orcid":false,"given":"Kingshuk","family":"Panda","sequence":"first","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4510-7963","authenticated-orcid":false,"given":"Maria J.","family":"Santiago","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"},{"name":"Department of Chemistry and Biochemistry, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1133-268X","authenticated-orcid":false,"given":"Md. Sohanur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0800-3970","authenticated-orcid":false,"given":"Suvankar","family":"Ghorai","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"},{"name":"Center for Translational Science, Florida International University, 11350 SW Village Parkway, Port St. Lucie, FL 34987, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2274-2454","authenticated-orcid":false,"given":"Irfan","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Environmental Medicine, University of Rochester Medical Center, 601 Elmwood Ave, Rochester, NY 14642, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoshang J.","family":"Unwalla","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5633-9749","authenticated-orcid":false,"given":"Srinivasan","family":"Chinnapaiyan","sequence":"additional","affiliation":[{"name":"Department of Cellular and Molecular Medicine, Herbert Wertheim College of Medicine, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1513\/pats.201009-059WR","article-title":"HIV-associated lung infections and complications in the era of combination antiretroviral therapy","volume":"8","author":"Crothers","year":"2011","journal-title":"Proc. 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