{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T18:46:20Z","timestamp":1791830780370,"version":"4.3.4"},"reference-count":48,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2026,10,13]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND:<\/jats:title>\n                    <jats:p>Pulmonary hypertension (PH) is a life-threatening cardiovascular disorder characterized by irreversible pulmonary vascular remodeling and poor prognosis. RNA pseudouridylation, the most evolutionarily conserved RNA epigenetic modification, and its catalytic enzyme pseudouridine synthase 7 (PUS7) remained uncharacterized in PH, representing a major gap in the understanding of the epigenetic pathogenesis of the disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS:<\/jats:title>\n                    <jats:p>We generated the first single-base resolution pseudouridine (\u03a8) landscape in lung tissues of patients with PH using bisulfite-induced deletion sequencing. PUS7 expression was analyzed in hypoxic pulmonary artery endothelial cells, the lung tissues of patients with PH, and SU5416-hypoxia rodent model. The functional roles of PUS7 were investigated through genetic manipulation (PUS7-deficiency cells, adeno-associated virus serotype\u2013mediated overexpression, endothelial cell\u2013specific knockdown, and heterozygous knockout mice) and pharmacological inhibition with NSC107512.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS:<\/jats:title>\n                    <jats:p>Bisulfite-induced deletion sequencing revealed global \u03a8 dysregulation in the lung tissues of patients with PH. Among PUS family members, PUS7 was the most markedly upregulated in these tissues and in the hypoxic pulmonary artery endothelial cells. Both gene knockdown and pharmacological inhibition with NSC107512 ameliorated PH, whereas adeno-associated virus serotype\u2013mediated PUS7 overexpression exacerbated disease progression. RNA immunoprecipitation sequencing and mutagenesis studies demonstrated that PUS7 bound to and catalyzed \u03a8 at position 688 of TGFBI (transforming growth factor \u03b2\u2013induced protein) mRNA, thereby stabilizing TGFBI and activating phosphatidylinositol 3-kinase\u2013protein kinase B signaling pathway. Furthermore, hypoxia-inducible factor 2\u03b1 bound directly to the PUS7 promoter, establishing a hypoxia-inducible factor 2\u03b1\/PUS7\/TGFBI\/phosphatidylinositol 3-kinase\u2013protein kinase B positive feedback loop that drives PH pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS:<\/jats:title>\n                    <jats:p>PUS7-mediated pseudouridylation serves as a novel epigenetic driver of PH through the hypoxia-inducible factor 2\u03b1\/PUS7\/TGFBI\/phosphatidylinositol 3-kinase\u2013protein kinase B axis, positioning PUS7 as a promising therapeutic target for this devastating disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circulationaha.126.080714","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T09:03:34Z","timestamp":1788253414000},"page":"1456-1472","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["PUS7-Mediated Pseudouridylation of TGFBI Drives Vascular Remodeling in Pulmonary Hypertension"],"prefix":"10.1161","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8830-628X","authenticated-orcid":true,"given":"Junting","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."},{"name":"Shenzhen Institute of Respiratory Disease, Shenzhen Key Laboratory of Respiratory Disease, Shenzhen People\u2019s Hospital (The Second Clinical Medical College, Jinan University; The First Affiliated Hospital, Southern University of Science and Technology), China (Y.L.)."},{"name":"Post-Doctoral Scientific Research Station of Basic Medicine, Jinan University, Guangzhou, China (Y.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhua","family":"He","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-1041-561X","authenticated-orcid":true,"given":"Jianxin","family":"Tan","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi, China (J.T., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Lung Transplant Group, Wuxi People\u2019s Hospital Affiliated to Nanjing Medical University, Wuxi, China (J.T., Y.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongbo","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9359-3943","authenticated-orcid":true,"given":"Fang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaolin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihui","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanbin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Joint Laboratory of Guangdong\u2013Hong Kong Universities for Vascular Homeostasis and Diseases (J.Z., Y.L., M.H., Z.L., H.W., F.L., X.C., Z.J., H.C., Z.C., F.K., J.F., J.-S.B.), SUSTech Homeostatic Medicine Institute, School of Medicine, Southern University of Science and Technology, Shenzhen, 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