{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T15:51:49Z","timestamp":1787500309530,"version":"build-2736575974"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    <jats:bold>Background:<\/jats:bold>\n                    Inhibiting proliferation and inducing apoptosis of myofibroblasts is becoming one of the promising and effective ways to treat hypertrophic scar. ABT-263, as an orally bioavailable BCL-2 family inhibitor, has showed great antitumor characteristics by targeting tumor cell apoptosis. The objective of this study was to explore whether ABT-263 could target apoptosis of overactivated myofibroblasts in hypertrophic scar.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods:<\/jats:bold>\n                    <jats:italic>In vivo<\/jats:italic>\n                    , we used ABT-263 to treat scars in a rabbit ear scar model. Photographs and ultrasound examination were taken weekly, and scars were harvested on day 42 for further Masson trichrome staining.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , the expression levels of BCL-2 family members, including prosurvival proteins, activators, and effectors, were detected systematically in hypertrophic scar tissues and adjacent normal skin tissues, as well as in human hypertrophic scar fibroblasts (HSFs) and human normal dermal fibroblasts (HFBs). The roles of ABT-263 in apoptosis and proliferation of HSFs and HFBs were determined by annexin V\/PI assay, CCK-8 kit, and cell cycle analysis. Mitochondrial membrane potential was evaluated by JC-1 staining and the expression of type I\/III collagen and \u03b1-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results:<\/jats:bold>\n                    <jats:italic>In vivo<\/jats:italic>\n                    , ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , the expression levels of BCL-2, BCL-XL, and BIM were significantly higher in scar tissues and HSFs than those in normal skin tissues and HFBs. ABT-263 selectively induced HSFs apoptosis by releasing BIM from binding with prosurvival proteins. Moreover, ABT-263 inhibited HSFs proliferation and reduced the expression of \u03b1-SMA and type I\/III collagen in a concentration- and time- dependent manner.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusion:<\/jats:bold>\n                    HSFs showed increased mitochondrial priming with higher level of proapoptotic activator BIM and were primed to death. ABT-263 showed great therapeutic ability in the treatment of hypertrophic scar by targeting HSFs.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2020.615505","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T05:48:46Z","timestamp":1610603326000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":22,"title":["ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts"],"prefix":"10.3389","volume":"11","author":[{"given":"Xiaolan","family":"Yang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongqiang","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chenjian","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Futing","family":"Shu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shichu","family":"Xiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongjun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaofan","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1007\/s40257-018-0358-5","article-title":"Acne scarring management: systematic review and evaluation of the evidence","volume":"19","author":"Bhargava","year":"2018","journal-title":"Am. J. Clin. Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s41038-015-0019-3","article-title":"Guidelines for burn rehabilitation in China","volume":"3","author":"Cen","year":"2015","journal-title":"Burns Trauma"},{"key":"B3","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1038\/nrm3722","article-title":"Control of apoptosis by the BCL-2 protein family: implications for physiology and therapy","volume":"15","author":"Czabotar","year":"2014","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1172\/jci28281","article-title":"Chronic lymphocytic leukemia requires BCL2 to sequester prodeath BIM, explaining sensitivity to BCL2 antagonist ABT-737","volume":"117","author":"Del Gaizo Moore","year":"2007","journal-title":"J. Clin. Invest"},{"key":"B5","doi-asserted-by":"publisher","first-page":"102715","DOI":"10.1016\/j.ebiom.2020.102715","article-title":"Targeted apoptosis of myofibroblasts by elesclomol inhibits hypertrophic scar formation","volume":"54","author":"Feng","year":"2020","journal-title":"EBioMedicine"},{"key":"B6","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1182\/blood.2019001545","article-title":"Combined inhibition of Bcl-2 and NF\u03baB synergistically induces cell death in cutaneous T-cell lymphomaCombined inhibition of Bcl-2 and NF\u03baB synergistically induces cell death in cutaneous T-cell lymphoma","volume":"134","author":"Froehlich","year":"2019","journal-title":"Blood"},{"key":"B7","doi-asserted-by":"publisher","first-page":"909","DOI":"10.1200\/jco.2010.31.6208","article-title":"Phase I study of Navitoclax (ABT-263), a novel Bcl-2 family inhibitor, in patients with small-cell lung cancer and other solid tumors","volume":"29","author":"Gandhi","year":"2011","journal-title":"J. Clin. Oncol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/j.retram.2016.09.003","article-title":"The role of myofibroblasts in wound healing","volume":"64","author":"Hinz","year":"2016","journal-title":"Curr. Res. Transl. Med"},{"key":"B9","doi-asserted-by":"crossref","DOI":"10.1002\/biof.1679","volume-title":"Nerolidol protects the liver against cyclophosphamide-induced hepatic inflammation, apoptosis, and fibrosis via modulation of Nrf2, NF-\u03baB p65, and caspase-3 signaling molecules in Swiss albino mice","author":"Iqubal","year":"2020"},{"key":"B10","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.matbio.2018.01.020","article-title":"BH3 mimetics as anti-fibrotic therapy: unleashing the mitochondrial pathway of apoptosis in myofibroblasts","author":"Kuehl","year":"2018","journal-title":"Matrix Biol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"eaal3765","DOI":"10.1126\/scitranslmed.aal3765","article-title":"Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis","volume":"9","author":"Lagares","year":"2017","journal-title":"Sci. Transl. Med"},{"key":"B12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1016\/j.jconrel.2019.05.038","article-title":"Strategy for hypertrophic scar therapy: improved delivery of triamcinolone acetonide using mechanically robust tip-concentrated dissolving microneedle array","volume":"306","author":"Lin","year":"2019","journal-title":"J. Contr. Release : Official Journal of the Controlled Release Society"},{"key":"B13","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1186\/s41038-018-0129-9","article-title":"Chinese expert consensus on clinical prevention and treatment of scar","volume":"6","author":"Lv","year":"2018","journal-title":"Burns & trauma"},{"key":"B14","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1002\/hep.29464","article-title":"Targeting senescent cholangiocytes and activated fibroblasts with B-cell lymphoma-extra large inhibitors ameliorates fibrosis in multidrug resistance 2 gene knockout (Mdr2 ) mice","volume":"67","author":"Moncsek","year":"2018","journal-title":"Hepatology (Baltimore, Md"},{"key":"B15","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1038\/nrd.2016.23","article-title":"Pioneering apoptosis-targeted cancer drug poised for FDA approval","volume":"15","author":"Mullard","year":"2016","journal-title":"Nat. Rev. Drug Discov"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1129","DOI":"10.1126\/science.1206727","article-title":"Pretreatment mitochondrial priming correlates with clinical response to cytotoxic chemotherapy","volume":"334","author":"Ni Chonghaile","year":"2011","journal-title":"Science"},{"key":"B17","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1016\/j.ijrobp.2017.02.216","article-title":"Inhibition of Bcl-2\/xl with ABT-263 selectively Kills senescent type II pneumocytes and reverses persistent pulmonary fibrosis induced by ionizing radiation in mice","volume":"99","author":"Pan","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. Phys"},{"key":"B18","doi-asserted-by":"publisher","first-page":"12895","DOI":"10.1073\/pnas.0914878107","article-title":"Heightened mitochondrial priming is the basis for apoptotic hypersensitivity of CD4+ CD8+ thymocytes","volume":"107","author":"Ryan","year":"2010","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"B19","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1001\/jama.283.1.69","article-title":"Long-term outcome of children surviving massive burns","volume":"283","author":"Sheridan","year":"2000","journal-title":"J. Am. Med. Assoc"},{"key":"B20","doi-asserted-by":"publisher","first-page":"1423","DOI":"10.1038\/s41374-018-0099-3","article-title":"Wild-type p53-modulated autophagy and autophagic fibroblast apoptosis inhibit hypertrophic scar formation","volume":"98","author":"Shi","year":"2018","journal-title":"Lab. Invest"},{"key":"B21","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/s0923-1811(99)00040-7","article-title":"Expression of Bcl-2, p53, c-jun and c-fos protooncogenes in keloids and hypertrophic scars","volume":"22","author":"Teofoli","year":"1999","journal-title":"J. Dermatol. Sci"},{"key":"B22","doi-asserted-by":"publisher","first-page":"350","DOI":"10.1513\/pats.200601-001TK","article-title":"Evolving concepts of apoptosis in idiopathic pulmonary fibrosis","volume":"3","author":"Thannickal","year":"2006","journal-title":"Proc. Am. Thorac. Soc"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3421","DOI":"10.1158\/0008-5472.can-07-5836","article-title":"ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor","volume":"68","author":"Tse","year":"2008","journal-title":"Canc. Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1016\/j.cell.2012.08.038","article-title":"Relative mitochondrial priming of myeloblasts and normal HSCs determines chemotherapeutic success in AML","volume":"151","author":"Vo","year":"2012","journal-title":"Cell"},{"key":"B25","doi-asserted-by":"publisher","first-page":"7145","DOI":"10.1182\/blood-2011-03-344812","article-title":"BCL2\/BCL-X(L) inhibition induces apoptosis, disrupts cellular calcium homeostasis, and prevents platelet activation","volume":"117","author":"Vogler","year":"2011","journal-title":"Blood"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1445","DOI":"10.1158\/1078-0432.ccr-15-0732","article-title":"A novel bioavailable BH3 mimetic efficiently inhibits colon cancer via cascade effects of mitochondria","volume":"22","author":"Wang","year":"2016","journal-title":"Clin. Canc. Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1016\/s1470-2045(10)70261-8","article-title":"Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity","volume":"11","author":"Wilson","year":"2010","journal-title":"Lancet Oncol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"5989","DOI":"10.2147\/ijn.s196794","article-title":"Cuprous oxide nanoparticles reduces hypertrophic scarring by inducing fibroblast apoptosis","volume":"14","author":"Xiao","year":"2019","journal-title":"Int. J. Nanomed"},{"key":"B29","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12989-020-00374-y","article-title":"Activation of synovial fibroblasts from patients at revision of their metal-on-metal total hip arthroplasty","volume":"17","author":"Xu","year":"2020","journal-title":"Part. Fibre Toxicol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1038\/nrm2308","article-title":"The BCL-2 protein family: opposing activities that mediate cell death","volume":"9","author":"Youle","year":"2008","journal-title":"Nat. Rev. Mol. Cell Biol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1186\/s13287-015-0133-y","article-title":"Intralesional injection of adipose-derived stem cells reduces hypertrophic scarring in a rabbit ear model","volume":"6","author":"Zhang","year":"2015","journal-title":"Stem Cell Res. Ther"},{"key":"B32","first-page":"5548","article-title":"A comparison of apoptosis levels in keloid tissue, physiological scars and normal skin","volume":"9","author":"Zhang","year":"2017","journal-title":"Am J Transl Res"},{"key":"B33","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.biomaterials.2016.10.031","article-title":"Topical administration of cryopreserved living micronized amnion accelerates wound healing in diabetic mice by modulating local microenvironment","volume":"113","author":"Zheng","year":"2017","journal-title":"Biomaterials"},{"key":"B34","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1016\/j.biopha.2018.01.158","article-title":"MicroRNA-519d inhibits proliferation and induces apoptosis of human hypertrophic scar fibroblasts through targeting Sirtuin 7","volume":"100","author":"Zhou","year":"2018","journal-title":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.615505\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T11:14:50Z","timestamp":1618830890000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2020.615505\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,14]]},"references-count":34,"alternative-id":["10.3389\/fphar.2020.615505"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2020.615505","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,1,14]]},"article-number":"615505"}}