{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T06:18:54Z","timestamp":1769149134078,"version":"3.49.0"},"reference-count":50,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T00:00:00Z","timestamp":1562630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01 HL086582"],"award-info":[{"award-number":["R01 HL086582"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012636","name":"New York State Stem Cell Science","doi-asserted-by":"publisher","award":["C30290GG"],"award-info":[{"award-number":["C30290GG"]}],"id":[{"id":"10.13039\/100012636","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":[[2019,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Collagen type III (COL3) is one of the 3 major collagens in the body, and loss of expression or mutations in the\n                    <jats:italic>COL3<\/jats:italic>\n                    gene have been associated with the onset of vascular diseases such the Ehlers\u2010Danlos syndrome. Previous work reported a significant reduction of COL3 in tissues such as skin and vessels with aging. In agreement, we found that COL3 was significantly reduced in senescent human mesenchymal stem cells and myofibroblasts derived from patients with Hutchinson\u2010Gilford progeria syndrome, a premature aging syndrome. Most notably, we discovered that ectopic expression of the embryonic transcription factor Nanog homeobox (NANOG) restored COL3 expression by restoring the activity of the TGF\u2010\u03b2 pathway that was impaired in senescent cells. RNA sequencing analysis showed that genes associated with the activation of the TGF\u2010\u03b2 pathway were up\u2010regulated, whereas negative regulators of the pathway were down\u2010regulated upon NANOG expression. Chromatin immunoprecipitation sequencing and immunoprecipitation experiments revealed that NANOG bound to the mothers against decapentaplegic (SMAD)2 and SMAD3 promoters, in agreement with increased expression and phosphorylation levels of both proteins. Using chemical inhibition, short hairpin RNA knockdown, and gain of function approaches, we established that both SMAD2 and SMAD3 were necessary to mediate the effects of NANOG, but SMAD3 overexpression was also sufficient for COL3 production. In summary, NANOG restored production of COL3, which was impaired by cellular aging, suggesting novel strategies to restore the impaired extracellular matrix production and biomechanical function of aged tissues, with potential implications for regenerative medicine and anti\u2010aging treatments.\u2014Rong, N., Mistriotis, P., Wang, X., Tseropoulos, G., Rajabian, N., Zhang, Y., Wang, J., Liu, S., Andreadis, S. T. Restoring extracellular matrix synthesis in senescent stem cells. FASEB J. 33, 10954\u201310965 (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.201900377r","type":"journal-article","created":{"date-parts":[[2019,7,9]],"date-time":"2019-07-09T17:35:42Z","timestamp":1562693742000},"page":"10954-10965","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Restoring extracellular matrix synthesis in senescent stem cells"],"prefix":"10.1096","volume":"33","author":[{"given":"Na","family":"Rong","sequence":"first","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Panagiotis","family":"Mistriotis","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgios","family":"Tseropoulos","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nika","family":"Rajabian","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yali","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianmin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Song","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stelios T.","family":"Andreadis","sequence":"additional","affiliation":[{"name":"Department of Chemical and Biological Engineering University at Buffalo Buffalo New York USA"},{"name":"Department of Biomedical Engineering University at Buffalo Buffalo New York USA"},{"name":"Center of Excellence in Bioinformatics and Life Sciences Buffalo New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,7,9]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1223"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.05.006"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000160548.78317.29"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.109.902056"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.11.1.18473"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.163592"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10522-015-9602-z"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/1047-8477(90)90110-X"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.5.1852"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.107.689208"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00223-014-9843-x"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000322399"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1098\/rsif.2012.1004"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200003093421001"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1086\/324123"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.31035"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvq024"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.2452"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2016.0494"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.teb.2012.0422"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.scr.2011.07.003"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2011.208"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051106"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708033200"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.72.10.8150-8157.1998"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-9-r137"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btv145"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp335"},{"key":"e_1_2_8_31_1","first-page":"13","article-title":"The content and ratio of type I and III collagen in skin differ with age and injury","volume":"10","author":"Cheng W.","year":"2011","journal-title":"Afr. J. Biotechnol."},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058000"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2015.05.006"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvs089"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.1992.81"},{"key":"e_1_2_8_36_1","doi-asserted-by":"crossref","first-page":"4692","DOI":"10.1038\/s41467-018-06654-8","article-title":"TGF-\u03b2-associated extracellular matrix genes link cancer-associated fibroblasts to immune evasion and immunotherapy failure","volume":"9","author":"Chakravarthy A.","year":"2018","journal-title":"Nat. Commun."},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.06.004"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature04915"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.11.019"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.052"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.06.020"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.05.039"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00197.2013"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.104380"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.116.304921"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0846.2001.007001018.x"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(01)00766-3"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.21255"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.109.136531"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43164"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-10-67"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900377R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.201900377R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.201900377R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:57:41Z","timestamp":1761681461000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.201900377R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,9]]},"references-count":50,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2019,10]]}},"alternative-id":["10.1096\/fj.201900377R"],"URL":"https:\/\/doi.org\/10.1096\/fj.201900377r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,9]]},"assertion":[{"value":"2019-02-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-06-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-07-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}