{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T12:33:17Z","timestamp":1786710797412,"version":"build-2736575974"},"reference-count":103,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T00:00:00Z","timestamp":1534377600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["K08DK101753"],"award-info":[{"award-number":["K08DK101753"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R03DK114464"],"award-info":[{"award-number":["R03DK114464"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM082852"],"award-info":[{"award-number":["R01GM082852"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The incidence and prevalence of inflammatory bowel disease (IBD) are increasing worldwide. IBD is known to be multifactorial, but inflammatory signaling within the intestinal epithelium and a subsequent failure of the intestinal epithelial barrier have been shown to play essential roles in disease pathogenesis. CaMKIV is a multifunctional protein kinase associated with inflammation and cell cycle regulation. CaMKIV has been extensively studied in autoimmune diseases, but a role in idiopathic intestinal inflammation has not been described. In this study, active CaMKIV was highly expressed within the intestinal epithelium of humans with ulcerative colitis and wild\u2010type (WT) mice with experimental induced colitis. Clinical disease severity directly correlates with CaMKIV activation, as does expression of proinflammatory cytokines and histologic features of colitis. In WT mice, CaMKIV activation is associated with increases in expression of 2 cell cycle proarrest signals: p53 and p21. Cell cycle arrest inhibits proliferation of the intestinal epithelium and ultimately results in compromised intestinal epithelial barrier integrity, further perpetuating intestinal inflammation during experimental colitis. Using a CaMKIV null mutant mouse, we demonstrate that a loss of CaMKIV protects against murine DSS colitis. Small molecules targeting CaMKIV activation may provide therapeutic benefit for patients with IBD.\u2014Cunningham, K. E., Novak, E. A., Vincent, G., Siow, V. S., Griffith, B. D., Ranganathan, S., Rosengart, M. R., Piganelli, J. D., Mollen, K. P. Calcium\/calmodulin\u2010dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis via inhibition of intestinal epithelial cell proliferation. FASEB J. 33, 1330\u20131346 (2019).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201800535r","type":"journal-article","created":{"date-parts":[[2018,8,16]],"date-time":"2018-08-16T13:55:01Z","timestamp":1534427701000},"page":"1330-1346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Calcium\/calmodulin\u2013dependent protein kinase IV (CaMKIV) activation contributes to the pathogenesis of experimental colitis\n                    <i>via<\/i>\n                    inhibition of intestinal epithelial cell proliferation"],"prefix":"10.1096","volume":"33","author":[{"given":"Kellie E.","family":"Cunningham","sequence":"first","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth A.","family":"Novak","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Division of Pediatric Surgery Children's Hospital of Pittsburgh University of Pitsburgh Medical Center (UPMC)  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garret","family":"Vincent","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Division of Pediatric Surgery Children's Hospital of Pittsburgh University of Pitsburgh Medical Center (UPMC)  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vei Shaun","family":"Siow","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian D.","family":"Griffith","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarangarajan","family":"Ranganathan","sequence":"additional","affiliation":[{"name":"Department of Pathology Children's Hospital of Pittsburgh University of Pitsburgh Medical Center (UPMC)  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Rosengart","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon D.","family":"Piganelli","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin P.","family":"Mollen","sequence":"additional","affiliation":[{"name":"Department of Surgery University of Pittsburgh School of Medicine  Pittsburgh Pennsylvania USA"},{"name":"Division of Pediatric Surgery Children's Hospital of Pittsburgh University of Pitsburgh Medical Center (UPMC)  Pittsburgh Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,8,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1423-0410.2010.01419.x"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i30.10262"},{"key":"e_1_2_9_4_1","volume-title":"The Facts about Inflammatory Bowel Disease","author":"Crohn's & Colitis Foundation of America","year":"2014"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.041"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2015.00062"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2016.169"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpgasthep0528"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.07.015"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2012.1969"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2010.869"},{"key":"e_1_2_9_12_1","first-page":"1357","article-title":"In vitro effects of dextran sulfate sodium on a Caco-2 cell line and plausible mechanisms for dextran sulfate sodium\u2010induced colitis","volume":"16","author":"Araki Y.","year":"2006","journal-title":"Oncol. Rep."},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pbiomolbio.2015.12.016"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2008.08.005"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M500067200"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.1.53"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.688812"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1995.1289"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.8.21.2527"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.20-17-06459.2000"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.231473998"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0761"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2005.03500.x"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2004.02873.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.2144\/99262bm05"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.75.11.5548"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a000935"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes8020066"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1218351"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-008-8086-2"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v22.i11.3117"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2012.06612.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep13262"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2013.09.001"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2008.08.027"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.04.033"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1089\/jir.2012.0031"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.180.8.5653"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.178.7.4641"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0085345"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1981.240.3.C96"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF01870778"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.87.3.736"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4827(76)90694-7"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.25.3.195"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.79.1.156"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1983.245.3.C203"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.22.1.173"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm.2016.23"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201601096RRR"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0925-4439(97)00061-6"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-4781(97)00035-3"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(04)00179-0"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2015.01.026"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00050.2008"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2008.07.021"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg2203"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2009.01.001"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10208"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2009.12.008"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI11476"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1212484110"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.01.023"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0088048"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.2010.207456"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175088"},{"key":"e_1_2_9_67_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)39106-9"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-biochem-072909-095555"},{"key":"e_1_2_9_69_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-physiol-030212-183707"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3606"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.588764"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a004424"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a008904"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.neo.7900101"},{"key":"e_1_2_9_75_1","first-page":"3311","article-title":"To arrest or not to G(2)-M Cell-cycle arrest: commentary re: A. K. Tyagi et al., Silibinin strongly synergizes human prostate carcinoma DU145 cells to doxorubicin-induced growth inhibition, G(2)-M arrest, and apoptosis. Clin. cancer res., 8: 3512\u20133519, 2002","volume":"8","author":"DiPaola R. S.","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-005-0050-3"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-0913"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.00051.2012"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.100281"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2006.11.001"},{"key":"e_1_2_9_81_1","first-page":"3198","article-title":"From intestinal stem cells to inflammatory bowel diseases","volume":"17","author":"Gersemann M.","year":"2011","journal-title":"World J. Gastroenterol."},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.010908.163145"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.05.009"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M302881200"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M079095"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1111\/imm.12309"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)80693-0"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.1.23-29.2002"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1997.7823"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804647"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/504638"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21077"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21379"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v16.i34.4264"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1002\/ibd.21403"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1002\/term.2506"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2013.73"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00535-015-1098-4"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.4172\/2161-069X.1000467"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0099293"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.4291\/wjgp.v7.i1.1"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2013.07.005"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11938-013-0008-1"},{"key":"e_1_2_9_104_1","unstructured":"The Jackson Laboratory.Stock number 009449 genotyping protocol. Accessed January 18 2018 at:https:\/\/www2.jax.org\/protocolsdb\/f?p=116:5:0::NO:5:P5_MASTER_PROTOCOL_ID P5_JRS_CODE:23048 004994"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201800535R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201800535R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201800535R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:46:04Z","timestamp":1786707964000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201800535R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,8,16]]},"references-count":103,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1096\/fj.201800535R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201800535r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,8,16]]},"assertion":[{"value":"2018-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-07-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-08-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}