{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:20:58Z","timestamp":1787869258397,"version":"build-2784847793"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004735","name":"Natural Science Foundation of\u00a0Hunan Province","doi-asserted-by":"publisher","award":["2021JJ30987"],"award-info":[{"award-number":["2021JJ30987"]}],"id":[{"id":"10.13039\/501100004735","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100019091","name":"Key Research and Development Program of Hunan Province of China","doi-asserted-by":"publisher","award":["2020sk 2056"],"award-info":[{"award-number":["2020sk 2056"]}],"id":[{"id":"10.13039\/501100019091","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012476","name":"Fundamental Research Funds for Central Universities of the Central South University","doi-asserted-by":"publisher","award":["Grant No. CX20220369"],"award-info":[{"award-number":["Grant No. CX20220369"]}],"id":[{"id":"10.13039\/501100012476","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Tissue Eng Regen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"Abstract<\/jats:title>\n \n BACKGROUND:<\/jats:italic><\/jats:bold>\n <\/jats:title>\n Oral submucous fibrosis (OSF) is a chronic disease with carcinogenic tendency that poses a non-negligible threat to human health. Exosomes derived from human adipose mesenchymal stem cells (ADSC-Exo) reduces visceral and cutaneous fibroses, but their role in OSF has received little attention. The aim of this study was to investigate the effects of ADSC-Exo on OSF and elucidate the mechanism.<\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:italic><\/jats:bold>\n <\/jats:title>\n In brief, ADSCs were extracted from adipose tissues and subjected to flow cytometry and induction culture. Fibroblasts were isolated from human buccal mucosa and subjected to immunofluorescence. Myofibroblasts were obtained from fibroblasts induced by arecoline and identified. Immunofluorescence assay confirmed that myofibroblasts could take up ADSC-Exo. The effects of ADSC-Exo on the proliferative and migratory capacities of myofibroblasts were examined using the Cell Counting Kit-8 and scratch assay. Real-time quantitative polymerase chain reaction (qPCR) was performed to evaluate mothers against decapentaplegic homolog 2 (Smad2), Smad3, Smad7, collagen type 1 (Col1), Col3, alpha smooth muscle actin (\u03b1-SMA), fibronectin, and vimentin. Western blotting was performed to detect phospho (p)-Smad2, Smad2, p-Smad2\/3, Smad2\/3, Smad7, Col1, Col3, \u03b1-SMA, fibronectin, and vimentin. Furthermore, the dual-luciferase reporter assay was performed to prove that miR-181a-5p in ADSC-Exo directly inhibited the expression of Smad2<\/jats:italic> mRNA to regulate the transforming growth factor beta (TGF-\u03b2) pathway. We also performed qPCR and western blotting to verify the results.<\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:italic><\/jats:bold>\n <\/jats:title>\n ADSC-Exo could promote the proliferation and migration of myofibroblasts, reduce the expressions of p-smad2, Smad2, p-smad2\/3, Smad2\/3, Col1, \u03b1SMA, fibronectin, and vimentin and elevated the levels of Smad7 and Col3. In addition, miR-181a-5p was highly expressed in ADSC-Exo and bound to the 3'-untranslated region of Smad2. ADSC-Exo enriched with miR-181a-5p reduced collagen production in myofibroblasts and modulated the TGF-\u03b2 pathway.<\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:italic><\/jats:bold>\n <\/jats:title>\n ADSC-Exo promoted the proliferative and migratory capacities of myofibroblasts and inhibited collagen deposition and trans-differentiation of myofibroblasts in vitro<\/jats:italic>. miR-181a-5p in exosomes targets Smad2 to regulate the TGF-\u03b2 pathway in myofibroblasts. ADSC-Exo perform antifibrotic actions through the miR-181a-5p\/Smad2 axis and may be a promising clinical treatment for OSF.<\/jats:p>\n <\/jats:sec>","DOI":"10.1007\/s13770-023-00579-0","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T15:02:10Z","timestamp":1695826930000},"page":"123-135","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Exosomes Derived from Human Adipose Mesenchymal Stem Cells Inhibits Fibrosis and Treats Oral Submucous Fibrosis via the miR-181a-5p\/Smad2 Axis"],"prefix":"10.1007","volume":"21","author":[{"given":"Zifei","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhao","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxi","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiyang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-4937","authenticated-orcid":false,"given":"Kun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"579_CR1","doi-asserted-by":"crossref","first-page":"1936","DOI":"10.1111\/odi.13727","volume":"27","author":"O Kujan","year":"2021","unstructured":"Kujan O, Mello FW, Warnakulasuriya S. Malignant transformation of oral submucous fibrosis: a systematic review and meta-analysis. Oral Dis. 2021;27:1936\u201346.","journal-title":"Oral Dis"},{"key":"579_CR2","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1111\/j.1600-0714.2005.00325.x","volume":"34","author":"P Rajalalitha","year":"2005","unstructured":"Rajalalitha P, Vali S. Molecular pathogenesis of oral submucous fibrosis\u2014a collagen metabolic disorder. J Oral Pathol Med. 2005;34:321\u20138.","journal-title":"J Oral Pathol Med"},{"key":"579_CR3","doi-asserted-by":"crossref","unstructured":"Zhang P, Chua N Q E, Dang S, Davis A, Chong KW, Prime SS, et al. Molecular mechanisms of malignant transformation of oral submucous fibrosis by different betel quid constituents-does fibroblast senescence play a role?. Int J Mol Sci. 2022;23:1637.","DOI":"10.3390\/ijms23031637"},{"key":"579_CR4","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1016\/j.oooo.2015.04.013","volume":"120","author":"B Liu","year":"2015","unstructured":"Liu B, Shen M, Xiong J, Yuan Y, Wu X, Gao X, et al. Synergistic effects of betel quid chewing, tobacco use (in the form of cigarette smoking), and alcohol consumption on the risk of malignant transformation of oral submucous fibrosis (OSF): a case-control study in Hunan Province, China. Oral Surg Oral Med Oral Pathol Oral Radiol. 2015;120:337\u201345.","journal-title":"Oral Surg Oral Med Oral Pathol Oral Radiol"},{"key":"579_CR5","first-page":"69","volume":"20","author":"YJ Hu","year":"2017","unstructured":"Hu YJ, Chen J, Zhong WS, Ling TY, Jian XC, Lu RH, et al. Trend analysis of betel nut-associated oral cancer and health burden in China. Chin J Dent Res. 2017;20:69\u201378.","journal-title":"Chin J Dent Res"},{"key":"579_CR6","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1111\/j.1600-0714.1994.tb00258.x","volume":"23","author":"R Maher","year":"1994","unstructured":"Maher R, Lee AJ, Warnakulasuriya KA, Lewis JA, Johnson NW. Role of areca nut in the causation of oral submucous fibrosis: a case-control study in Pakistan. J Oral Pathol Med. 1994;23:65\u20139.","journal-title":"J Oral Pathol Med"},{"key":"579_CR7","doi-asserted-by":"crossref","unstructured":"Shen Y W, Shih Y H, Fuh L J, Shieh TM. Oral submucous fibrosis: a review on biomarkers, pathogenic mechanisms, and treatments. Int J Mol Sci, 2020;21:7231.","DOI":"10.3390\/ijms21197231"},{"key":"579_CR8","doi-asserted-by":"crossref","unstructured":"Shih Y H, Wang T H, Shieh T M, Tseng YH. Oral submucous fibrosis: a review on etiopathogenesis, diagnosis, and therapy. Int J Mol Sci, 2019;20:2940.","DOI":"10.3390\/ijms20122940"},{"key":"579_CR9","doi-asserted-by":"crossref","first-page":"6721","DOI":"10.1002\/jcp.27418","volume":"234","author":"CY Fang","year":"2019","unstructured":"Fang CY, Hsia SM, Hsieh PL, Liao YW, Peng CY, Wu CZ, et al. Slug mediates myofibroblastic differentiation to promote fibrogenesis in buccal mucosa. J Cell Physiol. 2019;234:6721\u201330.","journal-title":"J Cell Physiol"},{"key":"579_CR10","doi-asserted-by":"crossref","first-page":"698","DOI":"10.1111\/jcmm.12219","volume":"18","author":"YC Chang","year":"2014","unstructured":"Chang YC, Tsai CH, Lai YL, Yu CC, Chi WY, Li JJ, et al. Arecoline-induced myofibroblast transdifferentiation from human buccal mucosal fibroblasts is mediated by ZEB1. J Cell Mol Med. 2014;18:698\u2013708.","journal-title":"J Cell Mol Med"},{"key":"579_CR11","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1002\/jcp.22142","volume":"224","author":"IT Lee","year":"2010","unstructured":"Lee IT, Lin CC, Wu YC, Yang CM. TNF-alpha induces matrix metalloproteinase-9 expression in A549 cells: role of TNFR1\/TRAF2\/PKCalpha-dependent signaling pathways. J Cell Physiol. 2010;224:454\u201364.","journal-title":"J Cell Physiol"},{"key":"579_CR12","doi-asserted-by":"crossref","first-page":"3666","DOI":"10.1073\/pnas.72.9.3666","volume":"72","author":"EA Carswell","year":"1975","unstructured":"Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975;72:3666\u201370.","journal-title":"Proc Natl Acad Sci USA"},{"key":"579_CR13","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1615\/CritRevEukarGeneExpr.v21.i1.40","volume":"21","author":"JA Arnott","year":"2011","unstructured":"Arnott JA, Lambi AG, Mundy C, Hendesi H, Pixley RA, Owen TA, et al. The role of connective tissue growth factor (CTGF\/CCN2) in skeletogenesis. Crit Rev Eukaryot Gene Expr. 2011;21:43\u201369.","journal-title":"Crit Rev Eukaryot Gene Expr"},{"key":"579_CR14","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1111\/odi.12845","volume":"24","author":"W Wang","year":"2018","unstructured":"Wang W, Xiong H, Hu Z, Zhao R, Hu Y, Chen W, et al. Experimental study on TGF-\u03b21-mediated CD147 expression in oral submucous fibrosis. Oral Dis. 2018;24:993\u20131000.","journal-title":"Oral Dis"},{"key":"579_CR15","doi-asserted-by":"crossref","first-page":"158","DOI":"10.3389\/fphar.2020.00158","volume":"11","author":"L Shukla","year":"2020","unstructured":"Shukla L, Yuan Y, Shayan R, Greening DW, Karnezis T. Fat therapeutics: the clinical capacity of adipose-derived stem cells and exosomes for human disease and tissue regeneration. Front Pharmacol. 2020;11:158.","journal-title":"Front Pharmacol"},{"key":"579_CR16","doi-asserted-by":"crossref","unstructured":"Lee S, Chae DS, Song BW, Lim S, Kim SW, Kim IK, et al. ADSC-based cell therapies for musculoskeletal disorders: a review of recent clinical trials. Int J Mol Sci, 2021;;22:10586.","DOI":"10.3390\/ijms221910586"},{"key":"579_CR17","doi-asserted-by":"crossref","first-page":"1292","DOI":"10.1016\/j.jhep.2019.01.030","volume":"70","author":"A Eguchi","year":"2019","unstructured":"Eguchi A, Kostallari E, Feldstein AE, Shah VH. Extracellular vesicles, the liquid biopsy of the future. J Hepatol. 2019;70:1292\u20134.","journal-title":"J Hepatol"},{"key":"579_CR18","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1681\/ASN.2012101031","volume":"24","author":"FT Borges","year":"2013","unstructured":"Borges FT, Melo SA, \u00d6zdemir BC, Kato N, Revuelta I, Miller CA, et al. TGF-\u03b21-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. J Am Soc Nephrol. 2013;24:385\u201392.","journal-title":"J Am Soc Nephrol"},{"key":"579_CR19","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1186\/s12943-018-0765-5","volume":"17","author":"H Liu","year":"2018","unstructured":"Liu H, Lei C, He Q, Zou Pan Z, Xiao D, Tao Y. Nuclear functions of mammalian MicroRNAs in gene regulation, immunity and cancer. Mol Cancer. 2018;17:64.","journal-title":"Mol Cancer"},{"key":"579_CR20","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.12659\/MSM.908056","volume":"24","author":"P Chen","year":"2018","unstructured":"Chen P, Pan J, Zhang X, Shi Z, Yang X. The role of microRNA-181a in myocardial fibrosis following myocardial infarction in a rat model. Med Sci Monit. 2018;24:4121\u20137.","journal-title":"Med Sci Monit"},{"key":"579_CR21","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1186\/s13287-019-1358-y","volume":"10","author":"P Hong","year":"2019","unstructured":"Hong P, Yang H, Wu Y, Li Kun, Tang Z. The functions and clinical application potential of exosomes derived from adipose mesenchymal stem cells: a comprehensive review. Stem Cell Res Ther. 2019;10:242.","journal-title":"Stem Cell Res Ther"},{"key":"579_CR22","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/cpr.12233","volume":"49","author":"Y Zhang","year":"2016","unstructured":"Zhang Y, Yu M, Tian W. Physiological and pathological impact of exosomes of adipose tissue. Cell Prolif. 2016;49:3\u201313.","journal-title":"Cell Prolif"},{"key":"579_CR23","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s11033-008-9235-2","volume":"36","author":"L Li","year":"2009","unstructured":"Li L, Zhang S, Zhang Y, et al. Paracrine action mediate the antifibrotic effect of transplanted mesenchymal stem cells in a rat model of global heart failure. Mol Biol Rep. 2009;36:725\u201331.","journal-title":"Mol Biol Rep"},{"key":"579_CR24","doi-asserted-by":"crossref","first-page":"32993","DOI":"10.1038\/srep32993","volume":"6","author":"L Hu","year":"2016","unstructured":"Hu L, Wang J, Zhou X, Xiong Z, Zhao J, Yu R, et al. Exosomes derived from human adipose mensenchymal stem cells accelerates cutaneous wound healing via optimizing the characteristics of fibroblasts. Sci Rep. 2016;6:32993.","journal-title":"Sci Rep"},{"key":"579_CR25","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.5966\/sctm.2015-0367","volume":"5","author":"S Fang","year":"2016","unstructured":"Fang S, Xu C, Zhang Y, Xue C, Yang C, Bi H, et al. Umbilical cord-derived mesenchymal stem cell-derived exosomal MicroRNAs suppress myofibroblast differentiation by inhibiting the transforming growth factor-\u03b2\/SMAD2 pathway during wound healing. Stem Cells Transl Med. 2016;5:1425\u201339.","journal-title":"Stem Cells Transl Med"},{"key":"579_CR26","doi-asserted-by":"crossref","unstructured":"Deng S, Zhou X, Ge Z, Song Y, Wang H, Liu X, et al. Exosomes from adipose-derived mesenchymal stem cells ameliorate cardiac damage after myocardial infarction by activating S1P\/SK1\/S1PR1 signaling and promoting macrophage M2 polarization. Int J Biochem Cell Biol. 2019;114:105564.","DOI":"10.1016\/j.biocel.2019.105564"},{"key":"579_CR27","doi-asserted-by":"crossref","unstructured":"Qu Y, Zhang Q, Cai X, Li F, Ma Z, Xu M, et al. Exosomes derived from miR-181-5p-modified adipose-derived mesenchymal stem cells prevent liver fibrosis via autophagy activation. J Cell Mol Med. 2017;21:2491\u2013502.","DOI":"10.1111\/jcmm.13170"},{"key":"579_CR28","doi-asserted-by":"crossref","unstructured":"Yu C C, Liao Y W, Hsieh P L, Li F, Ma Z, Xu M, Chang YC. Targeting lncRNA H19\/miR-29b\/COL1A1 axis impedes myofibroblast activities of precancerous oral submucous fibrosis. Int J Mol Sci. 2021;22:2216.","DOI":"10.3390\/ijms22042216"},{"key":"579_CR29","doi-asserted-by":"crossref","first-page":"102396","DOI":"10.1016\/j.autrev.2019.102396","volume":"18","author":"TW Henry","year":"2019","unstructured":"Henry TW, Mendoza FA, Jimenez SA. Role of microRNA in the pathogenesis of systemic sclerosis tissue fibrosis and vasculopathy. Autoimmun Rev. 2019;18:102396.","journal-title":"Autoimmun Rev"},{"key":"579_CR30","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1186\/s13287-021-02290-0","volume":"12","author":"Y Li","year":"2021","unstructured":"Li Y, Zhang J, Shi J, Liu K, Wang X, Jia Y, et al. Exosomes derived from human adipose mesenchymal stem cells attenuate hypertrophic scar fibrosis by miR-192-5p\/IL-17RA\/Smad axis. Stem Cell Res Ther. 2021;12:221.","journal-title":"Stem Cell Res Ther"},{"key":"579_CR31","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1089\/ten.tea.2017.0045","volume":"23","author":"M Dai","year":"2017","unstructured":"Dai M, Yu M, Zhang Y, Tian W. Exosome-like vesicles derived from adipose tissue provide biochemical cues for adipose tissue regeneration. Tissue Eng Part A. 2017;23:1221\u201330.","journal-title":"Tissue Eng Part A"},{"key":"579_CR32","doi-asserted-by":"crossref","unstructured":"Kalluri R, Lebleu V S.LeBleu VS. The biology, function, and biomedical applications of exosomes. Science. 2020;367:eaau6977.","DOI":"10.1126\/science.aau6977"},{"key":"579_CR33","doi-asserted-by":"crossref","first-page":"870","DOI":"10.1136\/thoraxjnl-2019-214077","volume":"75","author":"J Guiot","year":"2020","unstructured":"Guiot J, Cambier M, Boeckx A, Henket M, Nivelles O, Gester F, et al. Macrophage-derived exosomes attenuate fibrosis in airway epithelial cells through delivery of antifibrotic miR-142-3p. Thorax. 2020;75:870\u201381.","journal-title":"Thorax"},{"key":"579_CR34","doi-asserted-by":"crossref","first-page":"8613","DOI":"10.1002\/jcp.29706","volume":"235","author":"X Wan","year":"2020","unstructured":"Wan X, Chen S, Fang Y, Zuo W, Cui J, Xie S. Mesenchymal stem cell-derived extracellular vesicles suppress the fibroblast proliferation by downregulating FZD6 expression in fibroblasts via micrRNA-29b-3p in idiopathic pulmonary fibrosis. J Cell Physiol. 2020;235:8613\u201325.","journal-title":"J Cell Physiol"},{"key":"579_CR35","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1038\/nature07242","volume":"455","author":"D Baek","year":"2008","unstructured":"Baek D, Vill\u00e9n J, Shin C, Camargo FD, Gygi SP, Bartel DP. The impact of microRNAs on protein output. Nature. 2008;455:64\u201371.","journal-title":"Nature"},{"key":"579_CR36","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.yexcr.2018.06.035","volume":"370","author":"W Zhang","year":"2018","unstructured":"Zhang W, Bai X, Zhao B, Li Y, Zhang Y, Li Z, et al. Cell-free therapy based on adipose tissue stem cell-derived exosomes promotes wound healing via the PI3K\/Akt signaling pathway. Exp Cell Res. 2018;370:333\u201342.","journal-title":"Exp Cell Res"},{"key":"579_CR37","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1172\/JCI31487","volume":"117","author":"TA Wynn","year":"2007","unstructured":"Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest. 2007;117:524\u20139.","journal-title":"J Clin Invest"},{"key":"579_CR38","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1038\/s41586-020-2938-9","volume":"587","author":"NC Henderson","year":"2020","unstructured":"Henderson NC, Rieder F, Wynn TA. Fibrosis: from mechanisms to medicines. Nature. 2020;587:555\u201366.","journal-title":"Nature"},{"key":"579_CR39","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1038\/nrneph.2016.48","volume":"12","author":"XM Meng","year":"2016","unstructured":"Meng XM, Nikolic-Paterson DJ, Lan HY. TGF-\u03b2: the master regulator of fibrosis. Nat Rev Nephrol. 2016;12:325\u201338.","journal-title":"Nat Rev Nephrol"},{"key":"579_CR40","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1007\/s00441-011-1179-5","volume":"347","author":"H Ikushima","year":"2012","unstructured":"Ikushima H, Miyazono K. TGF-\u03b2 signal transduction spreading to a wider field: a broad variety of mechanisms for context-dependent effects of TGF-\u03b2. Cell Tissue Res. 2012;347:37\u201349.","journal-title":"Cell Tissue Res"},{"key":"579_CR41","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/cr.2008.327","volume":"19","author":"KH Wrighton","year":"2009","unstructured":"Wrighton KH, Lin X, Feng XH. Phospho-control of TGF-beta superfamily signaling. Cell Res. 2009;19:8\u201320.","journal-title":"Cell Res"},{"key":"579_CR42","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1038\/cr.2008.325","volume":"19","author":"CS Hill","year":"2009","unstructured":"Hill CS. Nucleocytoplasmic shuttling of Smad proteins. Cell Res. 2009;19:36\u201346.","journal-title":"Cell Res"},{"key":"579_CR43","first-page":"tr4","volume":"3","author":"JD Thatcher","year":"2010","unstructured":"Thatcher JD. The TGF-beta signal transduction pathway. Sci Signal. 2010;3:tr4.","journal-title":"Sci Signal"},{"key":"579_CR44","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1093\/abbs\/gmp018","volume":"41","author":"X Yan","year":"2009","unstructured":"Yan X, Liu Z, Chen Y. Regulation of TGF-beta signaling by Smad7. Acta Biochim Biophys Sin (Shanghai). 2009;41:263\u201372.","journal-title":"Acta Biochim Biophys Sin (Shanghai)"},{"key":"579_CR45","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cbi.2018.07.008","volume":"292","author":"HH Hu","year":"2018","unstructured":"Hu HH, Chen DQ, Wang YN, Feng YL, Cao G, Vaziri ND, et al. New insights into TGF-\u03b2\/Smad signaling in tissue fibrosis. Chem Biol Interact. 2018;292:76\u201383.","journal-title":"Chem Biol Interact"},{"key":"579_CR46","doi-asserted-by":"crossref","unstructured":"Humeres C, Shinde A V, Hanna A, Alex L, Hern\u00e1ndez SC, Li R, et al. Smad7 effects on TGF-\u03b2 and ErbB2 restrain myofibroblast activation and protect from postinfarction heart failure. J Clin Invest. 2022;132:e146926.","DOI":"10.1172\/JCI146926"},{"key":"579_CR47","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1080\/21623945.2022.2098583","volume":"11","author":"Q Niu","year":"2022","unstructured":"Niu Q, Wang T, Wang Z, Wang F, Huang D, Sun H, et al. Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease via delivering miR-223-3p. Adipocyte. 2022;11:572\u201387.","journal-title":"Adipocyte"},{"key":"579_CR48","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1186\/s13287-019-1332-8","volume":"10","author":"Y Yao","year":"2019","unstructured":"Yao Y, Chen R, Wang G, Zhang Y, Liu F. Exosomes derived from mesenchymal stem cells reverse EMT via TGF-\u03b21\/Smad pathway and promote repair of damaged endometrium. Stem Cell Res Ther. 2019;10:225.","journal-title":"Stem Cell Res Ther"},{"key":"579_CR49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.semcdb.2019.11.013","volume":"101","author":"KW Finnson","year":"2020","unstructured":"Finnson KW, Almadani Y, Philip A. Non-canonical (non-SMAD2\/3) TGF-\u03b2 signaling in fibrosis: mechanisms and targets. Semin Cell Dev Biol. 2020;101:115\u201322.","journal-title":"Semin Cell Dev Biol"},{"key":"579_CR50","doi-asserted-by":"crossref","first-page":"3050","DOI":"10.1242\/dev.137075","volume":"143","author":"JS Yu","year":"2016","unstructured":"Yu JS, Cui W. Proliferation, survival and metabolism: the role of PI3K\/AKT\/mTOR signalling in pluripotency and cell fate determination. Development. 2016;143:3050\u201360.","journal-title":"Development"},{"key":"579_CR51","doi-asserted-by":"crossref","first-page":"113729","DOI":"10.1016\/j.bcp.2019.113729","volume":"172","author":"FE Marquard","year":"2020","unstructured":"Marquard FE, J\u00fccker M. PI3K\/AKT\/mTOR signaling as a molecular target in head and neck cancer. Biochem Pharmacol. 2020;172:113729.","journal-title":"Biochem Pharmacol"},{"key":"579_CR52","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1007\/s00109-016-1441-0","volume":"94","author":"R Han","year":"2016","unstructured":"Han R, Ji X, Rong R, Li Y, Yao W, Yuan J, et al. MiR-449a regulates autophagy to inhibit silica-induced pulmonary fibrosis through targeting Bcl2. J Mol Med (Berl). 2016;94:1267\u201379.","journal-title":"J Mol Med (Berl)"},{"key":"579_CR53","doi-asserted-by":"crossref","first-page":"101600","DOI":"10.1016\/j.redox.2020.101600","volume":"36","author":"D Kong","year":"2020","unstructured":"Kong D, Zhang Z, Chen L, Huang W, Zhang F, Wang L, et al. Curcumin blunts epithelial-mesenchymal transition of hepatocytes to alleviate hepatic fibrosis through regulating oxidative stress and autophagy. Redox Biol. 2020;36:101600.","journal-title":"Redox Biol"},{"key":"579_CR54","doi-asserted-by":"crossref","first-page":"2835","DOI":"10.1681\/ASN.2013101068","volume":"25","author":"Y Ding","year":"2014","unstructured":"Ding Y, Kim SI, Lee SY, Koo JK, Wang Z, Choi ME. Autophagy regulates TGF-\u03b2 expression and suppresses kidney fibrosis induced by unilateral ureteral obstruction. J Am Soc Nephrol. 2014;25:2835\u201346.","journal-title":"J Am Soc Nephrol"},{"key":"579_CR55","doi-asserted-by":"crossref","first-page":"1859","DOI":"10.3892\/etm.2016.3145","volume":"11","author":"J Li","year":"2016","unstructured":"Li J, Zhao TT, Zhang P, Xu CJ, Rong ZX, Yan ZY, et al. Autophagy mediates oral submucous fibrosis. Exp Ther Med. 2016;11:1859\u201364.","journal-title":"Exp Ther Med"},{"key":"579_CR56","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.matbio.2018.02.004","volume":"68\u201369","author":"S Ricard-Blum","year":"2018","unstructured":"Ricard-Blum S, Baffet G, Th\u00e9ret N. Molecular and tissue alterations of collagens in fibrosis. Matrix Biol. 2018;68\u201369:122\u201349.","journal-title":"Matrix Biol"}],"container-title":["Tissue Engineering and Regenerative Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-023-00579-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s13770-023-00579-0\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s13770-023-00579-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T16:21:23Z","timestamp":1704298883000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s13770-023-00579-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,27]]},"references-count":56,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["579"],"URL":"https:\/\/doi.org\/10.1007\/s13770-023-00579-0","relation":{},"ISSN":["1738-2696","2212-5469"],"issn-type":[{"value":"1738-2696","type":"print"},{"value":"2212-5469","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,27]]},"assertion":[{"value":"18 May 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 July 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 July 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 September 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The cells (ADSC and fibroblasts) extracted from the adipose and oral buccal mucosa tissues in the experiment were obtained from the Xiangya Stomatological Hospital. All patients provided informed consent. Inclusion criteria were no systemic diseases, relevant family history, or current or recent medication. The study protocol was approved by the Ethics Committee of the Xiangya Stomatological Hospital of the Central South University. And the committee\u2019s reference number is 20220008.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics statements"}}]}}