{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T19:35:44Z","timestamp":1788204944556,"version":"build-2803163510"},"reference-count":25,"publisher":"The Company of Biologists","license":[{"start":{"date-parts":[[2021,5,18]],"date-time":"2021-05-18T00:00:00Z","timestamp":1621296000000},"content-version":"am","delay-in-days":503,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005089","name":"Beijing Municipal Natural Science Foundation","doi-asserted-by":"publisher","award":["No. 7163232 and No. S170003 to Y.X., No. S160004 to X.T."],"award-info":[{"award-number":["No. 7163232 and No. S170003 to Y.X., No. S160004 to X.T."]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Intrauterine growth retardation (IUGR) has high risk of developing bronchial asthma in childhood, whereas the underlying mechanisms remain unclear. This study aimed to disclose the role of vascular noninflammatory molecule 1 (vannin-1, encoded by the Vnn1 gene) and its downstream signaling in the IUGR asthmatic mice induced by ovalbumin. More significant histological alterations and increase of vannin-1 expressions were revealed in IUGR asthmatic mice, accompanied by elevated methylation of Vnn1 promoter regions. In IUGR asthmatic mice, we also found i) a direct binding of HNF4\u03b1 and PGC1\u03b1 to Vnn1 promoter by CHIP assay; ii) a direct interaction of HNF4\u03b1 with PGC1\u03b1; iii) upregulation of phospho-PI3K p85\/p55 and phospho-AktSer473 and downregulation of phospho-PTENTyr366; iv) increase in nuclear NF\u03baB p65 and decrease in cytosolic I\u03baB-\u03b1. In primary cultured bronchial epithelial cells derived from the IUGR asthmatic mice, knockdown of Vnn1 prevented upregulation of phospho-AktSer473 and increase of reactive oxygen species (ROS) and TGF-\u03b2 production. Taken together, we demonstrate that elevated vannin-1 activates the PI3K\/Akt\/NF\u03baB signaling pathway, leading to ROS and inflammation reactions responsible for asthma occurrence in IUGR. We also disclose that interaction of PGC1\u03b1 and HNF4\u03b1 promotes methylation of Vnn1 promoter regions and then upregulates vannin-1 expression.<\/jats:p>","DOI":"10.1242\/bio.049106","type":"journal-article","created":{"date-parts":[[2020,3,5]],"date-time":"2020-03-05T22:15:31Z","timestamp":1583446531000},"source":"Crossref","is-referenced-by-count":12,"title":["Methylated <i>Vnn1<\/i> at promoter regions induces asthma occurrence <i>via<\/i> the PI3K\/Akt\/NF\u03baB-mediated inflammation in the IUGR mice"],"prefix":"10.1242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9405-2025","authenticated-orcid":false,"given":"Yan","family":"Xing","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9867-2918","authenticated-orcid":false,"given":"Hongling","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4705-3444","authenticated-orcid":false,"given":"Xiumei","family":"Xiao","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2872-2737","authenticated-orcid":false,"given":"Zekun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1304-8639","authenticated-orcid":false,"given":"Hui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomei","family":"Tong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8371-4276","authenticated-orcid":false,"given":"Wei","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Peking University Third Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2020,1,1]]},"reference":[{"key":"2021042622411259300_BIO049106C1","doi-asserted-by":"publisher","first-page":"7214","DOI":"10.1128\/MCB.24.16.7214-7224.2004","article-title":"Vanin-1\u2212\/\u2212 mice exhibit a glutathione-mediated tissue resistance to oxidative stress","volume":"24","author":"Berruyer","year":"2004","journal-title":"Mol. 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