{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T07:58:50Z","timestamp":1790841530929,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pulm. circ."],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aimed to investigate the therapeutic effects of Poncirin on hypoxic pulmonary hypertension (HPH) and to elucidate the underlying mechanism, with a specific focus on transactive response DNA\u2010binding protein 43 (TDP43)\u2010mediated macrophage pyroptosis. A rat model of HPH was established using a hypobaric hypoxia chamber. In vitro, rat alveolar macrophages (NR8383 cells) and pulmonary artery smooth muscle cells (PASMCs) were cultured under normoxic or hypoxic (1% O\n                    <jats:sub>2<\/jats:sub>\n                    ) conditions. TDP43 expression was modulated through small interfering RNA (siRNA)\u2010mediated knockdown or lentivirus\u2010mediated overexpression. Poncirin was administered at a dose of 30\u2009mg\/kg in vivo and at a concentration of 50\u2009\u03bcM in vitro to assess its pharmacologic effects. The results demonstrated that TDP43 expression was markedly upregulated in lung tissues of rats with HPH and in hypoxia\u2010exposed NR8383 cells, and this was accompanied by increased macrophage accumulation around pulmonary arterioles. Hypoxia\u2010induced TDP43 upregulation promoted macrophage pyroptosis via activation of NLRP3, Caspase 1, and N\u2010GSDMD, leading to enhanced release of the inflammatory cytokine interleukin\u20101\u03b2 (IL\u20101\u03b2), which in turn facilitated PASMCs proliferation. Poncirin significantly attenuated hypoxia\u2010induced macrophage pyroptosis and PASMCs proliferation in both in vivo and in vitro models by downregulating TDP43 expression. Collectively, these findings identify TDP43 as a key mediator in the pathogenesis of HPH and support Poncirin as a potential therapeutic agent for HPH through targeting of TDP43\u2010mediated macrophage pyroptosis.\n                  <\/jats:p>","DOI":"10.1002\/pul2.70368","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T10:09:57Z","timestamp":1784628597000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Poncirin Alleviates Hypoxic Pulmonary Hypertension by Blocking TDP43\u2010Mediated Macrophage Pyroptosis"],"prefix":"10.1002","volume":"16","author":[{"given":"Jiao","family":"Yue","sequence":"first","affiliation":[{"name":"Department of Cardiology, The General Hospital of Western Theater Command, College of Medicine Southwest Jiaotong University Chengdu Sichuan 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