{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T14:29:47Z","timestamp":1777559387746,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T00:00:00Z","timestamp":1411948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning","award":["2012M3A9C6049728"],"award-info":[{"award-number":["2012M3A9C6049728"]}]},{"DOI":"10.13039\/501100002630","name":"Ewha Womans University","doi-asserted-by":"crossref","award":["RP-2013"],"award-info":[{"award-number":["RP-2013"]}],"id":[{"id":"10.13039\/501100002630","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal Cellular Physiology"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>CCN1 is highly expressed in cancer cells and has been identified in the secretome of bone marrow\u2010derived mesenchymal stem cells (BM\u2010MSC). Although secreted CCN1 is known to promote angiogenesis, its underlying mechanism remains unclear. Here, we examined whether our recently\u2010established tonsil\u2010derived MSC (T\u2010MSC) secrete CCN1 and, if any, how CCN1 promotes the angiogenesis of human umbilical vein endothelial cells (HUVEC). Compared with untreated control T\u2010MSC, a higher level of CCN1 was secreted by T\u2010MSC treated with activin A and sonic hedgehog, drugs known to induce endodermal differentiation. Expectedly, conditioned medium collected from differentiated T\u2010MSC (DCM) significantly increased HUVEC migration and tube formation compared with that from control T\u2010MSC (CCM), and these stimulatory effects were reversed by neutralization with anti\u2010CCN1 antibody. Treatment with recombinant human CCN1 (rh\u2010CCN1) alone also mimicked the stimulatory effects of DCM. Furthermore, treatment with either DCM or rh\u2010CCN1 increased the phosphorylation of AMP kinase (AMPK), and ectopic expression of siRNA of the AMPK gene inhibited all observed effects of both DCM and rh\u2010CCN1. However, no alteration of intracellular ATP levels or phosphorylation of LKB1, a well\u2010known upstream factor of AMPK activation, was observed under our conditions. Finally, the neutralization of integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> with anti\u2010integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> antibody almost completely reversed the effects of CCN1 on AMPK phosphorylation, and EC migration and tube formation. Taken together, we demonstrated that T\u2010MSC increase the secretion of CCN1 in response to endodermal differentiation and that integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> and AMPK mediate CCN1\u2010induced EC migration and tube formation independent of intracellular ATP levels alteration. J. Cell. Physiol. 230: 140\u2013149, 2015. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcp.24690","type":"journal-article","created":{"date-parts":[[2014,6,9]],"date-time":"2014-06-09T11:28:39Z","timestamp":1402313319000},"page":"140-149","source":"Crossref","is-referenced-by-count":34,"title":["CCN1 Secreted by Tonsil\u2010Derived Mesenchymal Stem Cells Promotes Endothelial Cell Angiogenesis via Integrin \u03b1<sub>v<\/sub>\u03b2<sub>3<\/sub> and AMPK"],"prefix":"10.1002","volume":"230","author":[{"given":"Yoon Shin","family":"Park","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soojin","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoon Mi","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yeonsil","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung\u2010Ae","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sung\u2010Chul","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Biochemistry School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyung\u2010Ha","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han Su","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology Head\u2010Neck Surgery School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inho","family":"Jo","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine School of Medicine and Global Top 5 Research Program Ewha Womans University Mok\u20106\u2010dong Yangcheon\u2010gu Seoul 158\u2010710 Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,9,29]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.11.6355"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2008.0337"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023823803510"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1780169"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1163"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058796"},{"key":"e_1_2_6_8_1","first-page":"S245","article-title":"Role of alpha v integrins during angiogenesis","volume":"6","author":"Eliceiri BP","year":"2000","journal-title":"Cancer J"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.21701"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/10430340260185094"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-3570"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.143.4.8731"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2008.07.006"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2013.12.011"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0031303"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-7843.2004.pto950502.x"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.5.3090"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-011-0778-3"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M209288200"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2004-0213"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1208238"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.24.8709-8720.2002"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300643200"},{"key":"e_1_2_6_24_1","first-page":"645","article-title":"Expression of the growth factor\u2010inducible immediate early gene cyr61 correlates with chondrogenesis during mouse embryonic development","volume":"3","author":"O'Brien TP","year":"1992","journal-title":"Cell Growth Differ"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.10.7.3569"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2000.tb06313.x"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.niox.2013.04.003"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2010.05.003"},{"key":"e_1_2_6_29_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.121.10.3163"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.3109\/14653249.2012.706708"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1186\/1478-811X-3-5"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000022200.71892.9F"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.8.2955-2964.2006"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.087122"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200504015"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11684-011-0164-4"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1006\/dbio.1997.8766"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M511178200"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M009755200"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yexcr.2008.08.001"}],"container-title":["Journal of Cellular Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjcp.24690","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcp.24690","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T06:05:29Z","timestamp":1696399529000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcp.24690"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,9,29]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2015,1]]}},"alternative-id":["10.1002\/jcp.24690"],"URL":"https:\/\/doi.org\/10.1002\/jcp.24690","archive":["Portico"],"relation":{},"ISSN":["0021-9541","1097-4652"],"issn-type":[{"value":"0021-9541","type":"print"},{"value":"1097-4652","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,9,29]]}}}