{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:57:40Z","timestamp":1793501860164,"version":"4.5.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"DOD Peer Reviewed Medical Research Program","award":["W81X WH-20-1-0142"],"award-info":[{"award-number":["W81X WH-20-1-0142"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL133067"],"award-info":[{"award-number":["HL133067"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES025815"],"award-info":[{"award-number":["ES025815"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"DOD Peer Reviewed Medical Research Program","award":["W81X WH-20-1-0142"],"award-info":[{"award-number":["W81X WH-20-1-0142"]}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["HL133067"],"award-info":[{"award-number":["HL133067"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES025815"],"award-info":[{"award-number":["ES025815"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.atsjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,1,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Impaired alveolar epithelial regeneration in patients with idiopathic pulmonary fibrosis (PF) or chronic obstructive pulmonary disease is attributed to telomere dysfunction in type II alveolar epithelial cells (A2Cs). Genetic susceptibility, aging, and toxicant exposures, including tobacco smoke (TS), contribute to telomere dysfunction in A2Cs. Here we investigated whether improvement of telomere function plays a role in CSP7 (Cav1 scaffolding domain peptide)\u2013mediated protection of A2Cs against ongoing senescence and apoptosis during bleomycin-induced PF as well as alveolar injury caused by chronic TS exposure. We found a significant telomere shortening in A2Cs isolated from idiopathic PF and chronic obstructive pulmonary disease lungs in line with other studies. These cells showed increased p53 in addition to its posttranslational modification with induction of activated caspase-3 and \u03b2-galactosidase, suggesting a p53-mediated loss of A2C renewal. Further, we found increased expression of SIAH-1, a p53-inducible E3 ubiquitin ligase known to downregulate TRF2 (telomere repeats binding factor 2). Consistent with the loss of TRF2 and upregulation of TRF1, TERT (telomerase reverse transcriptase) was downregulated in A2Cs. A2Cs from fibrotic lungs of mice repeatedly instilled with bleomycin or isolated from a chronic TS exposure\u2013induced lung injury model showed reduced telomere length; induction of p53, PAI-1, SIAH1, and TRF1; as well as loss of TRF2 and TERT, which were reversed in wild-type mice after treatment with CSP7. Interestingly, PAI-1\u2212\/\u2212 mice, or those lacking microRNA-34a expression in A2Cs, resisted telomere dysfunction, whereas uPA\u2212\/\u2212 mice failed to respond to CSP7 treatment, suggesting p53-microRNA-34a feed-forward induction and that the p53-uPA pathway contributes to telomere dysfunction.<\/jats:p>","DOI":"10.1165\/rcmb.2023-0453oc","type":"journal-article","created":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T10:57:55Z","timestamp":1726225075000},"page":"97-108","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":8,"title":["CSP7 Protects Alveolar Epithelial Cells by Targeting\n                    <i>p53<\/i>\n                    -Fibrinolytic Pathways During Lung Injuries"],"prefix":"10.1093","volume":"72","author":[{"given":"Bijesh","family":"Puthusseri","sequence":"first","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashoka Kumar","family":"Bhagavath","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Korir","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Shetty","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gretchen A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dorota L.","family":"Stankowska","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Genetics, University of North Texas Health Science Center, Fort Worth, Texas; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagarjun V.","family":"Konduru","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Tang","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sudhir","family":"Bolla","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Criner","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Marchetti","sequence":"additional","affiliation":[{"name":"Department of Thoracic Medicine and Surgery, Temple University, Philadelphia, Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Durgesh Nandini","family":"Das","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of Medicine, University of Texas Health Science Center at Tyler, Tyler, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreerama","family":"Shetty","sequence":"additional","affiliation":[{"name":"Texas Lung Injury Institute, Department of 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