{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,18]],"date-time":"2026-10-18T01:24:45Z","timestamp":1792286685971,"version":"4.4.0"},"reference-count":41,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T00:00:00Z","timestamp":1523836800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81274172"],"award-info":[{"award-number":["81274172"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81470003"],"award-info":[{"award-number":["81470003"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473267"],"award-info":[{"award-number":["81473267"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81503330"],"award-info":[{"award-number":["81503330"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2018,7]]},"abstract":"Abstract<\/jats:title>\n \n Chronic obstructive pulmonary disease (\n COPD<\/jats:styled-content>\n ) is characterized by persistent airflow limitation and abnormal inflammatory response. Wnt\/\u03b2\u2010catenin and\n AMP<\/jats:styled-content>\n \u2010activated protein kinase (\n AMPK<\/jats:styled-content>\n ) have been shown to modulate lung inflammatory responses and injury. However, it remains elusive whether Wnt\/\u03b2\u2010catenin and\n AMPK<\/jats:styled-content>\n modulate nuclear factor erythroid\u20102 related factor\u20102 (Nrf2)\u2010mediated protective responses during the development of emphysema. Here we showed that treatment with a Wnt pathway activator (LiCl) reduced elastase\u2010induced airspace enlargement and cigarette smoke extract (\n CSE<\/jats:styled-content>\n )\u2010induced lung inflammatory responses in\n WT<\/jats:styled-content>\n mice, which was associated with increased activation of Nrf2 pathway. Interestingly, these effects of LiCl were not observed in Nrf2\n \u2212\/\u2212<\/jats:sup>\n mice exposed to elastase. In normal human bronchial epithelial (\n NHBE<\/jats:styled-content>\n ) cells, Wnt3a overexpression up\u2010regulated, whereas Wnt3a knockdown further down\u2010regulated the levels of Nrf2 and its target proteins heme oxygenase\u20101 (\n HO<\/jats:styled-content>\n \u20101) and\n NAD<\/jats:styled-content>\n (P)H: quinone oxidoreductase 1 (\n NQO<\/jats:styled-content>\n 1) by\n CSE<\/jats:styled-content>\n treatment. In contrast, Nrf2 deficiency did not have any effects on Wnt\/\u03b2\u2010catenin pathway in mouse lungs and\n NHBE<\/jats:styled-content>\n cells. Both elastase and\n CSE<\/jats:styled-content>\n exposures reduced\n AMPK<\/jats:styled-content>\n phosphorylation. A specific\n AMPK<\/jats:styled-content>\n activator metformin increased Wnt3a, \u03b2\u2010catenin, Nrf2 phosphorylation and activation but reduced the levels of\n IL<\/jats:styled-content>\n \u20106 and\n IL<\/jats:styled-content>\n \u20108 in\n NHBE<\/jats:styled-content>\n cells and mouse lungs exposed to\n CSE<\/jats:styled-content>\n . Furthermore, Nrf2 deficiency abolished the protection of metformin against\n CSE<\/jats:styled-content>\n \u2010induced increase in\n IL<\/jats:styled-content>\n \u20106 and\n IL<\/jats:styled-content>\n \u20108 in\n NHBE<\/jats:styled-content>\n cells. In conclusion, Nrf2 mediates the protective effects of both Wnt3a\/\u03b2\u2010catenin and\n AMPK<\/jats:styled-content>\n on lung inflammatory responses during the development of\n COPD<\/jats:styled-content>\n \/emphysema. These findings provide potential therapeutic targets for the intervention of\n COPD<\/jats:styled-content>\n \/emphysema.\n <\/jats:p>","DOI":"10.1111\/jcmm.13628","type":"journal-article","created":{"date-parts":[[2018,4,16]],"date-time":"2018-04-16T11:18:13Z","timestamp":1523877493000},"page":"3514-3525","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":119,"title":["Nrf2 attenuates inflammatory response in\n COPD<\/scp>\n \/emphysema: Crosstalk with Wnt3a\/\u03b2\u2010catenin and\n AMPK<\/scp>\n pathways"],"prefix":"10.1111","volume":"22","author":[{"given":"Wenhui","family":"Cui","sequence":"first","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Second Affiliated Hospital of Dalian Medical University Dalian Liaoning China"},{"name":"General Hospital of Datong Coal Mining Group Datong Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Zhang","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Second Affiliated Hospital of Dalian Medical University Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Panpan","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Dalian Medical University Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiao","family":"Qu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Dalian Medical University Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoting","family":"Mo","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wencheng","family":"Zhou","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Xu","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Yao","sequence":"additional","affiliation":[{"name":"Department of Critical Care and Pulmonary Medicine Shanxi Medical University Second Hospital Taiyuan Shanxi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4613-9652","authenticated-orcid":false,"given":"Jian","family":"Gao","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Anhui Medical University Hefei Anhui China"},{"name":"Second Affiliated Hospital of Dalian Medical University Dalian Liaoning China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,16]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201701-0218PP"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2009.10.022"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.05.016"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-015-0060-y"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.200910-1560OC"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2443.2005.00905.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.175.10.6968"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200421146"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0804333106"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2014.6040"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.00118-16"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24881"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI60132"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2008.070765"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00011-015-0878-x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2013-0505OC"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2007-0342OC"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2012.5116"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.15116"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13518"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S138006"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.04.029"},{"key":"e_1_2_7_24_1","first-page":"772","article-title":"WNT1\u2010inducible signaling protein\u20101 mediates pulmonary fibrosis in mice and is upregulated in humans with idiopathic pulmonary fibrosis","volume":"119","author":"Konigshoff M","year":"2009","journal-title":"J Clin Invest"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201605-0904OC"},{"key":"e_1_2_7_26_1","first-page":"657","article-title":"Elastase\u2010induced parenchymal disruption and airway hyper responsiveness in mouse precision cut lung slices: toward an ex vivo COPD model","volume":"7","author":"Dijk EM","year":"2016","journal-title":"Front Physiol"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2016.00457"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002142"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2012-0524OC"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1369\/0022155415600032"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0134492"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2015.06.002"},{"key":"e_1_2_7_33_1","first-page":"127","article-title":"AMP\u2010activated protein kinase: structure, function, and role in pathological processes","volume":"80","author":"Novikova DS","year":"2015","journal-title":"Biochemistry"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2003.11.005"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.25844"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.4046\/trd.2015.78.1.8"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M802537200"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00165.2014"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2013.03.022"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.199372"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2010.03.161"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1159\/000107058"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjcmm.13628","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13628","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.13628","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.13628","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,19]],"date-time":"2023-08-19T16:14:25Z","timestamp":1692461665000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.13628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,16]]},"references-count":41,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2018,7]]}},"alternative-id":["10.1111\/jcmm.13628"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.13628","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,16]]},"assertion":[{"value":"2017-04-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-03-09","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-16","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}