{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T17:22:11Z","timestamp":1793726531832,"version":"4.6.1"},"reference-count":42,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2022,5,5]],"date-time":"2022-05-05T00:00:00Z","timestamp":1651708800000},"content-version":"vor","delay-in-days":124,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005230","name":"Natural Science Foundation of Chongqing Municipality","doi-asserted-by":"publisher","award":["cstc2019jcyj-zdxmX0031"],"award-info":[{"award-number":["cstc2019jcyj-zdxmX0031"]}],"id":[{"id":"10.13039\/501100005230","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2019M653832XB"],"award-info":[{"award-number":["2019M653832XB"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Oxidative Medicine and Cellular Longevity"],"published-print":{"date-parts":[[2022,1]]},"abstract":"<jats:p>The \u201cobesity paradox in acute respiratory distress syndrome\u201d (ARDS) refers to the phenomenon in which obesity is associated with higher morbidity but lower mortality in patients with ARDS. Endothelial\u2010to\u2010mesenchymal transition (EndMT) represents a key link in the interaction between endothelial disruption and mesenchymal fibrosis under inflammatory and oxidative conditions, which represent the intersectional pathophysiology of ARDS. Adipose tissue is considered to constitute the major source of circulating exosomal microRNAs (miRNAs), which act as genetic forms of adipokines for cell\u2013cell crosstalk. We aimed to demonstrate the regulation and mechanism of adipose\u2010derived exosomes in the obesity paradox in ARDS. High\u2010fat\u2010induced obese mice and lean control mice were subjected to ARDS insult to investigate the effects of obesity on ARDS and microarray analysis was performed to screen for differences in circulating miRNAs. In addition, mice and pulmonary endothelial cells were administered with adipose\u2010derived exosomal miR\u2010122\u20105p to investigate the underlying molecular mechanisms. We found high\u2010fat diet\u2010induced obesity protected against ARDS in mice by reinforcing endothelial barrier and attenuating fibroproliferation. Circulating exosomes produced in the obese state mediated these protective effects by inhibiting EndMT and oxidative stress. Mechanistically, adipose\u2010derived exosomal miR\u2010122\u20105p promoted the integrity and function of pulmonary endothelial barrier and alleviated fibrogenesis by suppressing EndMT and oxidative stress through down\u2010regulation of the transforming growth factor <jats:italic>\u03b2<\/jats:italic>1 (TGF\u2010<jats:italic>\u03b2<\/jats:italic>1)\/TGF\u2010<jats:italic>\u03b2<\/jats:italic> receptor 1 (TGF\u2010<jats:italic>\u03b2<\/jats:italic>R1)\/Smad2 pathway <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro.<\/jats:italic> In conclusion, adipose\u2010derived circulating exosomal miR\u2010122\u20105p protects against ARDS by reinforcing pulmonary endothelial barrier through inhibition of EndMT and oxidative stress via down\u2010regulation of the TGF\u2010<jats:italic>\u03b2<\/jats:italic> pathway, which propose a potential explanation for the obesity paradox in ARDS and indicate promising prospects for adipose\u2010derived exosomes in cell\u2010free therapies for ARDS.<\/jats:p>","DOI":"10.1155\/2022\/5475832","type":"journal-article","created":{"date-parts":[[2022,5,6]],"date-time":"2022-05-06T03:05:07Z","timestamp":1651806307000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Adipose\u2010Derived Circulating Exosomes Promote Protection of the Pulmonary Endothelial Barrier by Inhibiting EndMT and Oxidative Stress through Down\u2010Regulation of the TGF\u2010<i>\u03b2<\/i> Pathway: A Potential Explanation for the Obesity Paradox in 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