{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T14:55:34Z","timestamp":1787237734019,"version":"build-2736575974"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T00:00:00Z","timestamp":1715126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32060207"],"award-info":[{"award-number":["32060207"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Qinghai Provincial Department of Science and Technology Project","award":["2021-ZJ-738"],"award-info":[{"award-number":["2021-ZJ-738"]}]},{"DOI":"10.13039\/501100010230","name":"Qinghai University","doi-asserted-by":"publisher","award":["No.2022-KF-03"],"award-info":[{"award-number":["No.2022-KF-03"]}],"id":[{"id":"10.13039\/501100010230","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Hypoxic pulmonary hypertension (HPH) is characterized by progressive pulmonary vasoconstriction, vascular remodeling, and right ventricular hypertrophy, causing right heart failure. This study aimed to investigate the therapeutic effects of exosomes from Tibetan umbilical cord mesenchymal stem cells on HPH via the TGF-\u03b21\/Smad2\/3 pathway, comparing them with exosomes from Han Chinese individuals. An HPH rat model was established in vivo, and a hypoxia-induced injury in the rat pulmonary artery smooth muscle cells (rPASMCs) was simulated in vitro. Exosomes from human umbilical cord mesenchymal stem cells were administered to HPH model rats or added to cultured rPASMCs. The therapeutic effects of Tibetan-mesenchymal stem cell-derived exosomes (Tibetan-MSC-exo) and Han-mesenchymal stem cell-derived exosomes (Han-MSC-exo) on HPH were investigated through immunohistochemistry, western blotting, EdU, and Transwell assays. The results showed that Tibetan-MSC-exo significantly attenuated pulmonary vascular remodeling and right ventricular hypertrophy in HPH rats compared with Han-MSC-exo. Tibetan-MSC-exo demonstrated better inhibition of hypoxia-induced rPASMCs proliferation and migration. Transcriptome sequencing revealed upregulated genes (Nbl1, Id2, Smad6, and Ltbp1) related to the TGF\u03b2 pathway. Nbl1 knockdown enhanced hypoxia-induced rPASMCs proliferation and migration, reversing Tibetan-MSC-exo-induced downregulation of TGF\u03b21 and p-Smad2\/3. Furthermore, TGF\u03b21 overexpression hindered the therapeutic effects of Tibetan-MSC-exo and Han-MSC-exo on hypoxic injury. These findings suggest that Tibetan-MSC-exo favors HPH treatment better than Han-MSC-exo, possibly through the modulation of the TGF\u03b21\/Smad2\/3 pathway via Nbl1.<\/jats:p>","DOI":"10.1093\/stmcls\/sxae032","type":"journal-article","created":{"date-parts":[[2024,5,8]],"date-time":"2024-05-08T09:07:22Z","timestamp":1715159242000},"page":"720-735","source":"Crossref","is-referenced-by-count":8,"title":["Tibetan mesenchymal stem cell-derived exosomes alleviate pulmonary vascular remodeling in hypoxic pulmonary hypertension rats"],"prefix":"10.1093","volume":"42","author":[{"given":"Qingqing","family":"Zhang","sequence":"first","affiliation":[{"name":"Research Center for High Altitude Medicine, Qinghai University , Xining 810001, People\u2019s Republic of China"},{"name":"Key Laboratory of High Altitude Medicine (Ministry of Education) , Xining 810001, People\u2019s Republic of China"},{"name":"Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai 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