ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts
Background: 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 o...
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| Format: | Article |
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.615505/full |
| _version_ | 1828978074547388416 |
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| author | Xiaolan Yang Xiaolan Yang Xiaolan Yang Xiaolan Yang Yongqiang Xiao Yongqiang Xiao Chenjian Zhong Chenjian Zhong Futing Shu Shichu Xiao Yongjun Zheng Zhaofan Xia Zhaofan Xia Zhaofan Xia |
| author_facet | Xiaolan Yang Xiaolan Yang Xiaolan Yang Xiaolan Yang Yongqiang Xiao Yongqiang Xiao Chenjian Zhong Chenjian Zhong Futing Shu Shichu Xiao Yongjun Zheng Zhaofan Xia Zhaofan Xia Zhaofan Xia |
| author_sort | Xiaolan Yang |
| collection | DOAJ |
| description | Background: 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.Methods:In vivo, 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. In vitro, 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 α-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism.Results:In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis. In vitro, 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 α-SMA and type I/III collagen in a concentration- and time- dependent manner.Conclusion: 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. |
| first_indexed | 2024-12-14T15:10:57Z |
| format | Article |
| id | doaj.art-bc76330c32e74fc28dfde8e329a4bcd6 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-14T15:10:57Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-bc76330c32e74fc28dfde8e329a4bcd62022-12-21T22:56:34ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.615505615505ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of MyofibroblastsXiaolan Yang0Xiaolan Yang1Xiaolan Yang2Xiaolan Yang3Yongqiang Xiao4Yongqiang Xiao5Chenjian Zhong6Chenjian Zhong7Futing Shu8Shichu Xiao9Yongjun Zheng10Zhaofan Xia11Zhaofan Xia12Zhaofan Xia13Department of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaFujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou, ChinaResearch Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, ChinaQuanzhou First Hospital Affiliated to Fujian Medical University, Fujian, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Burn and Plastic Surgery, The 970th Hospital of People’s Liberation Army, Yantai, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaFujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaDepartment of Burn Surgery, Changhai Hospital, Naval Medical University, Shanghai, ChinaFujian Burn Institute, Fujian Medical University Union Hospital, Fuzhou, ChinaResearch Unit of Key Techniques for Treatment of Burns and Combined Burns and Trauma Injury, Chinese Academy of Medical Sciences, Shanghai, ChinaBackground: 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.Methods:In vivo, 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. In vitro, 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 α-SMA was measured by PCR, western blotting, and immunofluorescence staining. Furthermore, immunoprecipitation was performed to explore the potential mechanism.Results:In vivo, ABT-263 could significantly improve the scar appearance and collagen arrangement, decrease scar elevation index (SEI), and induce cell apoptosis. In vitro, 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 α-SMA and type I/III collagen in a concentration- and time- dependent manner.Conclusion: 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.https://www.frontiersin.org/articles/10.3389/fphar.2020.615505/fullABT-263hypertrophic scarapoptosismyofibroblastskin |
| spellingShingle | Xiaolan Yang Xiaolan Yang Xiaolan Yang Xiaolan Yang Yongqiang Xiao Yongqiang Xiao Chenjian Zhong Chenjian Zhong Futing Shu Shichu Xiao Yongjun Zheng Zhaofan Xia Zhaofan Xia Zhaofan Xia ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts Frontiers in Pharmacology ABT-263 hypertrophic scar apoptosis myofibroblast skin |
| title | ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts |
| title_full | ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts |
| title_fullStr | ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts |
| title_full_unstemmed | ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts |
| title_short | ABT-263 Reduces Hypertrophic Scars by Targeting Apoptosis of Myofibroblasts |
| title_sort | abt 263 reduces hypertrophic scars by targeting apoptosis of myofibroblasts |
| topic | ABT-263 hypertrophic scar apoptosis myofibroblast skin |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.615505/full |
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