{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T22:45:25Z","timestamp":1793745925889,"version":"4.6.1"},"reference-count":36,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,25]],"date-time":"2023-09-25T00:00:00Z","timestamp":1695600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hainan Provincial Natural Science Foundation of China","award":["322RC773"],"award-info":[{"award-number":["322RC773"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["321QN320"],"award-info":[{"award-number":["321QN320"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["1630032023009"],"award-info":[{"award-number":["1630032023009"]}]},{"name":"Hainan Provincial Natural Science Foundation of China","award":["HNARS2022-2-G3"],"award-info":[{"award-number":["HNARS2022-2-G3"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["322RC773"],"award-info":[{"award-number":["322RC773"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["321QN320"],"award-info":[{"award-number":["321QN320"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["1630032023009"],"award-info":[{"award-number":["1630032023009"]}]},{"name":"Central Public-interest Scientific Institution Basal Research Fund","award":["HNARS2022-2-G3"],"award-info":[{"award-number":["HNARS2022-2-G3"]}]},{"name":"Hainan Modern Agricultural Production Research System","award":["322RC773"],"award-info":[{"award-number":["322RC773"]}]},{"name":"Hainan Modern Agricultural Production Research System","award":["321QN320"],"award-info":[{"award-number":["321QN320"]}]},{"name":"Hainan Modern Agricultural Production Research System","award":["1630032023009"],"award-info":[{"award-number":["1630032023009"]}]},{"name":"Hainan Modern Agricultural Production Research System","award":["HNARS2022-2-G3"],"award-info":[{"award-number":["HNARS2022-2-G3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Intestinal vessels play a critical role in nutrient absorption, whereas the effect and mechanism of low birth weight (LBW) on its formation remain unclear. Here, twenty newborn piglets were assigned to the control (CON) group (1162 \u00b1 98 g) and LBW group (724 \u00b1 31 g) according to their birth weight. Results showed that the villus height and the activity of maltase in the jejunum were lower in the LBW group than in the CON group. LBW group exhibited a higher oxidative stress level and impaired mitochondrial function in the jejunum and was lower than the CON group in the intestinal vascular density. To investigate the role of oxidative stress in intestinal angiogenesis, H2O2 was employed to induce oxidative stress in porcine intestinal epithelial cells (IPEC-J2). The results showed that the conditioned media from IPEC-J2 with H2O2 treatment decreased the angiogenesis of porcine vascular endothelial cells (PVEC). Transcriptome analysis revealed that a higher expression level of dual oxidase 2 (DUOX2) was found in the intestine of LBW piglets. Knockdown of DUOX2 in IPEC-J2 increased the proliferation and decreased the oxidative stress level. In addition, conditioned media from IPEC-J2 with DUOX2-knockdown was demonstrated to promote the angiogenesis of PVEC. Mechanistically, the knockdown of DUOX2 decreased the reactive oxygen species (ROS) level, thus increasing the angiogenesis in a matrix metalloproteinase 3 (MMP3) dependent manner. Conclusively, our results indicated that DUOX2-induced oxidative stress inhibited intestinal angiogenesis through MMP3 in a LBW piglet model.<\/jats:p>","DOI":"10.3390\/antiox12101800","type":"journal-article","created":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T03:53:00Z","timestamp":1695700380000},"page":"1800","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["DUOX2-Induced Oxidative Stress Inhibits Intestinal Angiogenesis through MMP3 in a Low-Birth-Weight Piglet Model"],"prefix":"10.3390","volume":"12","author":[{"given":"Dongbin","family":"Zou","sequence":"first","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"},{"name":"College of Life Sciences, Hainan University, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun","family":"Yang","sequence":"additional","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"},{"name":"College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengjie","family":"Ji","sequence":"additional","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renlong","family":"Lv","sequence":"additional","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tieshan","family":"Xu","sequence":"additional","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6406-6445","authenticated-orcid":false,"given":"Chengjun","family":"Hu","sequence":"additional","affiliation":[{"name":"Tropical Crop Genetic Resource Research Institute, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1186\/s13643-021-01730-5","article-title":"Low birth weight as a predictor of adverse health outcomes during adulthood in twins: A systematic review and meta-analysis","volume":"10","author":"Hassan","year":"2021","journal-title":"Syst. Rev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1093\/carcin\/bgaa056","article-title":"DUOX2 promotes the progression of colorectal cancer cells by regulating the AKT pathway and interacting with RPL3","volume":"42","author":"Zhang","year":"2021","journal-title":"Carcinogenesis"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"769734","DOI":"10.3389\/fmed.2021.769734","article-title":"Prematurity and low birth weight in neonates as a risk factor for obesity, hypertension, and chronic kidney disease in pediatric and adult age","volume":"8","author":"Grillo","year":"2021","journal-title":"Front. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"109912","DOI":"10.1016\/j.celrep.2021.109912","article-title":"Fetal growth restriction impairs hippocampal neurogenesis and cognition via Tet1 in offspring","volume":"37","author":"Chen","year":"2021","journal-title":"Cell Rep."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Xiong, L., You, J., Zhang, W., Zhu, Q., Blachier, F., Yin, Y., and Kong, X. (2020). Intrauterine growth restriction alters growth performance, plasma hormones, and small intestinal microbial communities in growing-finishing pigs. J. Anim. Sci. Biotechnol., 11.","DOI":"10.1186\/s40104-020-00490-x"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/jn\/nxz016","article-title":"N-carbamylglutamate and L-arginine promote intestinal absorption of amino acids by regulating the mTOR signaling pathway and amino acid and peptide transporters in suckling lambs with intrauterine growth restriction","volume":"149","author":"Zhang","year":"2019","journal-title":"J. Nutr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1095\/biolreprod.111.096198","article-title":"Effect of the anti-oxidant tempol on fetal growth in a mouse model of fetal growth restriction","volume":"87","author":"Stanley","year":"2012","journal-title":"Biol. Reprod."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, T., Huang, S., Lei, L., Tao, S., Xiong, Y., Wu, G., Hu, J., Yuan, X., Zhao, S., and Zuo, B. (2021). Intrauterine growth restriction alters nutrient metabolism in the intestine of porcine offspring. J. Anim. Sci. Biotechnol., 12.","DOI":"10.1186\/s40104-020-00538-y"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Chen, Y., Zhang, H., Chen, Y., Jia, P., Ji, S., Zhang, Y., and Wang, T. (2021). Resveratrol and its derivative pterostilbene ameliorate intestine injury in intrauterine growth-retarded weanling piglets by modulating redox status and gut microbiota. J. Anim. Sci. Biotechnol., 12.","DOI":"10.1186\/s40104-021-00589-9"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1875","DOI":"10.1007\/s00394-021-02783-x","article-title":"Effect of maternal curcumin supplementation on intestinal damage and the gut microbiota in male mice offspring with intra-uterine growth retardation","volume":"61","author":"Qi","year":"2022","journal-title":"Eur. J. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1182\/blood-2013-09-512749","article-title":"Oxidative stress in angiogenesis and vascular disease","volume":"123","author":"Kim","year":"2014","journal-title":"Blood"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1007\/s00394-017-1539-3","article-title":"Effects of dietary L-methionine supplementation on intestinal integrity and oxidative status in intrauterine growth-retarded weanling piglets","volume":"57","author":"Su","year":"2018","journal-title":"Eur. J. Nutr."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.redox.2017.11.001","article-title":"\u03b1-Lipoic acid improves abnormal behavior by mitigation of oxidative stress, inflammation, ferroptosis, and tauopathy in P301S Tau transgenic mice","volume":"14","author":"Zhang","year":"2018","journal-title":"Redox Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1016\/j.cmet.2010.08.016","article-title":"Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice","volume":"12","author":"Ragni","year":"2010","journal-title":"Cell Metab."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"2709","DOI":"10.1007\/s00394-020-02461-4","article-title":"A maternal high-fat\/low-fiber diet impairs glucose tolerance and induces the formation of glycolytic muscle fibers in neonatal offspring","volume":"60","author":"Hu","year":"2021","journal-title":"Eur. J. Nutr."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2481592","DOI":"10.1155\/2019\/2481592","article-title":"Maternal diet-induced obesity compromises oxidative stress status and angiogenesis in the porcine placenta by upregulating Nox2 expression","volume":"2019","author":"Hu","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Taylor, J.P., and Tse, H.M. (2021). The role of NADPH oxidases in infectious and inflammatory diseases. Redox Biol., 48.","DOI":"10.1016\/j.redox.2021.102159"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"skab255","DOI":"10.1093\/jas\/skab255","article-title":"Effects of Bacillus subtilis on jejunal integrity, redox status, and microbial composition of intrauterine growth restriction suckling piglets","volume":"99","author":"Yun","year":"2021","journal-title":"J. Anim. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.aninu.2020.12.009","article-title":"Dietary dihydroartemisinin supplementation alleviates intestinal inflammatory injury through TLR4\/NOD\/NF-\u03baB signaling pathway in weaned piglets with intrauterine growth retardation","volume":"7","author":"Niu","year":"2021","journal-title":"Anim. Nutr."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1016\/j.tcb.2018.08.001","article-title":"The intestinal stem cell niche: Homeostasis and adaptations","volume":"28","author":"Santos","year":"2018","journal-title":"Trends Cell Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"561","DOI":"10.3389\/fphys.2020.00561","article-title":"Transcriptome differences suggest novel mechanisms for intrauterine growth restriction mediated dysfunction in small intestine of neonatal piglets","volume":"11","author":"Huang","year":"2020","journal-title":"Front. Physiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1080\/1745039X.2017.1312812","article-title":"Effects of medium-chain triglycerides on intestinal morphology and energy metabolism of intrauterine growth retarded weanling piglets","volume":"71","author":"Zhang","year":"2017","journal-title":"Arch. Anim. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7591840","DOI":"10.1155\/2019\/7591840","article-title":"Resveratrol attenuates oxidative stress-induced intestinal barrier injury through PI3K\/Akt-mediated Nrf2 signaling pathway","volume":"2019","author":"Zhuang","year":"2019","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/s41385-018-0021-8","article-title":"NADPH oxidases and ROS signaling in the gastrointestinal tract","volume":"11","author":"Aviello","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/s00428-003-0903-2","article-title":"Levels of oxidative stress and redox-related molecules in the placenta in preeclampsia and fetal growth restriction","volume":"444","author":"Takagi","year":"2004","journal-title":"Virchows Arch."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123349","DOI":"10.1016\/j.jhazmat.2020.123349","article-title":"Exposure to copper oxide nanoparticles triggers oxidative stress and endoplasmic reticulum (ER)-stress induced toxicology and apoptosis in male rat liver and BRL-3A cell","volume":"401","author":"Liu","year":"2021","journal-title":"J. Hazard. Mater."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"153309","DOI":"10.1016\/j.tox.2022.153309","article-title":"Ochratoxin A induces cytotoxicity through ROS-mediated endoplasmic reticulum stress pathway in human gastric epithelium cells","volume":"479","author":"Wang","year":"2022","journal-title":"Toxicology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1152\/physrev.00040.2012","article-title":"Oxidative stress: An essential factor in the pathogenesis of gastrointestinal mucosal diseases","volume":"94","author":"Bhattacharyya","year":"2014","journal-title":"Physiol. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1111\/j.1749-6632.2009.05046.x","article-title":"Mitochondria and hypoxic signaling: A new view","volume":"1177","author":"Poyton","year":"2009","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Hu, C., Wu, Z., Huang, Z., Hao, X., Wang, S., Deng, J., Yin, Y., and Tan, C. (2021). Nox2 impairs VEGF-A-induced angiogenesis in placenta via mitochondrial ROS-STAT3 pathway. Redox Biol., 45.","DOI":"10.1016\/j.redox.2021.102051"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"7178123","DOI":"10.1155\/2020\/7178123","article-title":"Protective effect of polydatin on jejunal mucosal integrity, redox status, inflammatory response, and mitochondrial function in intrauterine growth-retarded weanling piglets","volume":"2020","author":"Zhang","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Yang, L.Q., Yu, S.P., Yang, Y.T., Zhao, Y.S., Wang, F.Y., Chen, Y., Li, Q.H., Tian, P., Zhu, Y.Y., and Zhang, J.G. (2021). Muscone derivative ZM-32 inhibits breast tumor angiogenesis by suppressing HuR-mediated VEGF and MMP9 expression. Biomed. Pharmacother., 136.","DOI":"10.1016\/j.biopha.2021.111265"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/j.jocn.2019.02.019","article-title":"Oxidative stress-induced angiogenesis","volume":"63","author":"Huang","year":"2019","journal-title":"J. Clin. Neurosci."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"111495","DOI":"10.1016\/j.yexcr.2019.111495","article-title":"SIX4 activates Akt and promotes tumor angiogenesis","volume":"383","author":"Sun","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"eabj8393","DOI":"10.1126\/scisignal.abj8393","article-title":"STAT3-YAP\/TAZ signaling in endothelial cells promotes tumor angiogenesis","volume":"14","author":"Shen","year":"2021","journal-title":"Sci. Signal."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Saleh, A., Stathopoulou, M.G., Dad\u00e9, S., Ndiaye, N.C., Azimi-Nezhad, M., Murray, H., Masson, C., Lamont, J., Fitzgerald, P., and Visvikis-Siest, S. (2015). Angiogenesis related genes NOS3, CD14, MMP3 and IL4R are associated to VEGF gene expression and circulating levels in healthy adults. BMC Med. Genet., 16.","DOI":"10.1186\/s12881-015-0234-6"}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/10\/1800\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:57:46Z","timestamp":1760129866000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/12\/10\/1800"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,25]]},"references-count":36,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["antiox12101800"],"URL":"https:\/\/doi.org\/10.3390\/antiox12101800","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,25]]}}}