{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:17:14Z","timestamp":1792664234909,"version":"4.5.0"},"reference-count":75,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2014,4]]},"abstract":"<jats:title>Significance<\/jats:title>\n                  <jats:p>Here, we show how, mechanistically, inflammation-recruited macrophages may stimulate beta-cell proliferation in the pancreas, and specifically identify that TGF\u03b21 and EGF, which are secreted by M2 macrophages, induce SMAD7 expression in beta cells. SMAD7 not only activates cell cycle activators but also induces the nuclear exclusion of cell cycle inhibitors to promote beta-cell replication. Our study thus reveals a molecular pathway to induce beta-cell proliferation through enhanced SMAD7 activity specifically in beta cells.<\/jats:p>","DOI":"10.1073\/pnas.1321347111","type":"journal-article","created":{"date-parts":[[2014,3,18]],"date-time":"2014-03-18T01:41:09Z","timestamp":1395106869000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":254,"title":["M2 macrophages promote beta-cell proliferation by up-regulation of SMAD7"],"prefix":"10.1073","volume":"111","author":[{"given":"Xiangwei","family":"Xiao","sequence":"first","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iljana","family":"Gaffar","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Guo","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wiersch","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shane","family":"Fischbach","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren","family":"Peirish","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zewen","family":"Song","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yousef","family":"El-Gohary","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krishna","family":"Prasadan","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiyo","family":"Shiota","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George K.","family":"Gittes","sequence":"additional","affiliation":[{"name":"Division of Pediatric Surgery, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh School of Medicine, Pittsburgh, PA 15224"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2014,3,17]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/dmr.5610080303"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.arcmed.2005.03.014"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature02520"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2007.04.011"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1369"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI22098"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI66323"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1210\/er.2006-0004"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.120.12.3451"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.15.1866"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.143.3.827"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2013.04.003"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1880"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.0040039"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2337\/db12-1428"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0432"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20101827"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1998.9170"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2007.02.015"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80303-7"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00432-X"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.01636-06"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/39348"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.13.7.804"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/17826"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.01.022"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.14.2.187"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508977103"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri3070"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2808"},{"key":"e_1_3_3_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri1733"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1038\/nri2528"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.10.036"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.484022"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0848"},{"key":"e_1_3_3_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2009.11.003"},{"key":"e_1_3_3_37_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.056499"},{"key":"e_1_3_3_38_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043959"},{"key":"e_1_3_3_39_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.053843"},{"key":"e_1_3_3_40_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI29988"},{"key":"e_1_3_3_41_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.090159"},{"key":"e_1_3_3_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.015"},{"key":"e_1_3_3_43_2","doi-asserted-by":"publisher","DOI":"10.2337\/db08-1198"},{"key":"e_1_3_3_44_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.9.2557"},{"key":"e_1_3_3_45_2","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0160"},{"key":"e_1_3_3_46_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI69468"},{"key":"e_1_3_3_47_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00217308"},{"key":"e_1_3_3_48_2","doi-asserted-by":"publisher","DOI":"10.1081\/LPR-120004780"},{"key":"e_1_3_3_49_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.422949"},{"key":"e_1_3_3_50_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.25.9.3752-3762.2005"},{"key":"e_1_3_3_51_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2009-0057"},{"key":"e_1_3_3_52_2","doi-asserted-by":"publisher","DOI":"10.4161\/cc.5.3.2399"},{"key":"e_1_3_3_53_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jviromet.2012.04.004"},{"key":"e_1_3_3_54_2","doi-asserted-by":"publisher","DOI":"10.4161\/bioe.22293"},{"key":"e_1_3_3_55_2","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.2013.113"},{"key":"e_1_3_3_56_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.12.2617"},{"key":"e_1_3_3_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2010.02.008"},{"key":"e_1_3_3_58_2","doi-asserted-by":"publisher","DOI":"10.2337\/db06-0413"},{"key":"e_1_3_3_59_2","doi-asserted-by":"publisher","DOI":"10.1038\/39369"},{"key":"e_1_3_3_60_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm010493y"},{"key":"e_1_3_3_61_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.1.65"},{"key":"e_1_3_3_62_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.62.1.58"},{"key":"e_1_3_3_63_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2005.12.009"},{"key":"e_1_3_3_64_2","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.12035"},{"key":"e_1_3_3_65_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2013-1463"},{"key":"e_1_3_3_66_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.482"},{"key":"e_1_3_3_67_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1492"},{"key":"e_1_3_3_68_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M003282200"},{"key":"e_1_3_3_69_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M002815200"},{"key":"e_1_3_3_70_2","first-page":"9","article-title":"Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads","volume":"38","author":"Park SH","year":"2005","unstructured":"SH Park, Fine tuning and cross-talking of TGF-beta signal by inhibitory Smads. J Biochem Mol Biol 38, 9\u201316 (2005).","journal-title":"J Biochem Mol Biol"},{"key":"e_1_3_3_71_2","doi-asserted-by":"publisher","DOI":"10.1038\/ni1451"},{"key":"e_1_3_3_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/35085597"},{"key":"e_1_3_3_73_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101672200"},{"key":"e_1_3_3_74_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI64095"},{"key":"e_1_3_3_75_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.07.029"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.1321347111","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T23:13:53Z","timestamp":1649805233000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.1321347111"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,17]]},"references-count":75,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2014,4]]}},"alternative-id":["10.1073\/pnas.1321347111"],"URL":"https:\/\/doi.org\/10.1073\/pnas.1321347111","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,17]]},"assertion":[{"value":"2014-03-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}