{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T01:05:15Z","timestamp":1767920715125,"version":"3.49.0"},"reference-count":42,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T00:00:00Z","timestamp":1589414400000},"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":["81573652"],"award-info":[{"award-number":["81573652"]}],"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":["81874354"],"award-info":[{"award-number":["81874354"]}],"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":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The expression of C\u2010terminal phosphorylated Smad3 (pSmad3C) is down\u2010regulated with the progression of liver disease. Thus, we hypothesized that pSmad3C expression may be negatively related to liver disease. To develop novel therapeutic strategies, a suitable animal model is required that will allow researchers to study the effect of Smad3 domain\u2010specific phosphorylation on liver disease progression. The current study aimed to construct a new mouse model with the Smad3 C\u2010terminal phosphorylation site mutation and to explore the effects of this mutation on CCl<jats:sub>4<\/jats:sub>\u2010induced inflammation. Smad3 C\u2010terminal phosphorylation site mutant mice were generated using TetraOne\u2122 gene fixed\u2010point knock\u2010in technology and embryonic stem cell microinjection. Resulting mice were identified by genotyping, and the effects on inflammation were explored in the presence or absence of CCl<jats:sub>4<\/jats:sub>. No homozygous mice were born, indicating that the mutation is embryonic lethal. There was no significant difference in liver phenotype and growth between the wild\u2010type (WT) and heterozygous (HT) mice in the absence of reagent stimulation. After CCl<jats:sub>4<\/jats:sub>\u2010induced acute and chronic liver damage, liver pathology, serum transaminase (ALT\/AST) expression and levels of inflammatory factors (IL\u20106\/TNF\u2010\u03b1) were more severely altered in HT mice than in WT mice. Furthermore, pSmad3C protein levels were lower in liver tissue from HT mice. These results suggest that Smad3 C\u2010terminal phosphorylation may have a protective effect during the early stages of liver injury. In summary, we have generated a new animal model that will be a novel tool for future research on the effects of Smad3 domain\u2010specific phosphorylation on liver disease progression.<\/jats:p>","DOI":"10.1111\/jcmm.15385","type":"journal-article","created":{"date-parts":[[2020,5,14]],"date-time":"2020-05-14T08:50:01Z","timestamp":1589446201000},"page":"7044-7054","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Smad3 gene C\u2010terminal phosphorylation site mutation aggravates CCl<sub>4<\/sub>\u2010induced inflammation in mice"],"prefix":"10.1111","volume":"24","author":[{"given":"Hanyan","family":"Ding","sequence":"first","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meng","family":"Fang","sequence":"additional","affiliation":[{"name":"Department of Anatomy Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongfang","family":"Gong","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dong","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guanghua","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chao","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingjing","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4183-826X","authenticated-orcid":false,"given":"Yan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Key Laboratory of Anti\u2010inflammatory and Immunopharmacology Ministry of Education Anhui Medical University Hefei China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2017.00461"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2018.02.090"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2015.04.013"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306842"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2018.07.008"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgr172"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.12259"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2014.2552"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(00)80061-1"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204117"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00432-X"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.cellbio.21.022404.142018"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M909467199"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.24.6.2546-2559.2004"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.98.3.992"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00298-3"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02554"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20400"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22765"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/jgh.12490"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1615\/CritRevEukarGeneExpr.v17.i4.30"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-013-0910-2"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm5010007"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.22.4.599"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-7128-2_8"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.5.1280"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81730-4"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6101(99)00028-3"},{"key":"e_1_2_8_30_1","first-page":"825","article-title":"Construction and functional study of three plasmids including Smad3 WT, Smad3 EPSM and Smad3 3S\u2010A stably transfected HepG2 cell lines","volume":"32","author":"Wu JJ","year":"2016","journal-title":"Chin Pharmacol Bull"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-4629"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.22.12595"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/jca.20906"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3667"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nutres.2008.02.001"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.injury.2009.02.023"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2016.11.006"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21674"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700630"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0156090"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2012.00053"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-011-1246-y"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1734"}],"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.15385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15385","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.15385","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15385","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T12:11:45Z","timestamp":1694002305000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.15385"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,14]]},"references-count":42,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1111\/jcmm.15385"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.15385","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,14]]},"assertion":[{"value":"2019-07-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-14","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}