Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice
文献类型：期刊论文
| 作者 | Samarawickrama, Priyadarshani Nadeeshika5,6,7; Zhang, Guiqin4; Zhu, Enfang4; Dong, Xin6,7; Nisar, Ayesha6,7; Zhu, Hong4; Ma, Yuan3; Zhou, Zheyan2; Yang, Honglin3; Gui, Li4 |
| 刊名 | THERANOSTICS
 |
| 出版日期 | 2024 |
| 卷号 | 14期号:14页码:5429-5442 |
| 关键词 | cellular senescence diabetic foot ulcer imaging senolytic wound healing |
| ISSN号 | 1838-7640 |
| DOI | 10.7150/thno.100991 |
| 通讯作者 | Li, Wen(wenli_wli@163.com) ; He, Yonghan(heyonghan@mail.kiz.ac.cn) |
| 英文摘要 | Background: Diabetic foot ulcers (DFUs) pose a substantial healthcare challenge due to their high rates of morbidity, recurrence, disability, and mortality. Current DFU therapeutics continue to grapple with multiple limitations. Senescent cells (SnCs) have been found to have a beneficial effect on acute wound healing, however, their roles in chronic wounds, such as DFU, remain unclear. Methods and results: We collected skin, fat, and muscle samples from clinical patients with DFU and lower limb fractures. RNA-sequencing combined with qPCR analyses on these samples demonstrate a significant accumulation of SnCs at DFU, as indicated by higher senescence markers (e.g., p16 and p21) and a senescence-associated secretory phenotype (SASP). We constructed a type 2 diabetic model of db/db mice, fed with a high-fat diet (Db-HFD), which were wounded using a 6 mm punch to the dorsal skin. HFD slightly affected wound healing in wild-type (WT) mice, but high glucose significantly delayed wound healing in the Db-HFD mice. We injected the mice with a previously developed fluorescent probe (XZ1208), which allows the detection of SnCs in vivo, and observed a strong senescence signal at the wound site of the Db-HFD mice. Contrary to the beneficial effects of SnCs in acute wound healing, our results demonstrated that clearance of SnCs using the senolytic compound ABT263 significantly accelerated wound healing in Db-HFD mice. Conclusion: Collectively, these findings suggest that SnCs critically accumulate at wound sites, delaying the healing process in DFUs. Thus, targeting SnCs with senolytic therapy represents a promising approach for DFU treatment, potentially improving the quality of life for patients with DFUs. |
| WOS关键词 | CELLULAR SENESCENCE ; MECHANISMS |
| 资助项目 | National Key R&D Program of China[2023YFC3603300] ; National Natural Science Foundation of China[82360717] ; National Natural Science Foundation of China[82171558] ; Yunnan Fundamental Research Projects[202101BA070001-110] ; Yunnan Fundamental Research Projects[202201AS070038] ; Yunnan Fundamental Research Projects[202305AH340006] ; Yunnan Fundamental Research Projects[202401CF070064] ; State Key Laboratory for Conservation and Utilization of Bio-Resources in Yunnan[2023KF008] ; Scientific Research Project of Yunnan Provincial Department of Education[2024Y923] ; Pioneer Hundred Talents Program of the Chinese Academy of Sciences ; Yunnan Revitalization Talent Support Program Young Talent Project |
| WOS研究方向 | Research & Experimental Medicine |
| 语种 | 英语 |
| WOS记录号 | WOS:001312857600005 |
| 出版者 | IVYSPRING INT PUBL |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/313633]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Li, Wen; He, Yonghan |
| 作者单位 | 1.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Dev Ctr, Shanghai, Peoples R China 2.Third Peoples Hosp Yunnan Prov, Dept Pathol, Kunming 650011, Yunnan, Peoples R China 3.Third Peoples Hosp Yunnan Prov, Dept Orthoped, Kunming 650011, Yunnan, Peoples R China 4.Dali Univ, Affiliated Hosp 2, Peoples Hosp Yunnan Prov 3, Dept Endocrinol, Kunming 650011, Yunnan, Peoples R China 5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 6.Chinese Acad Sci, Kunming Inst Zool, Key Lab Hlth Aging Res Yunnan Prov, Kunming 650201, Yunnan, Peoples R China 7.Chinese Acad Sci, Kunming Inst Zool, Key Lab Genet Evolut & Anim Models, Kunming 650201, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Samarawickrama, Priyadarshani Nadeeshika,Zhang, Guiqin,Zhu, Enfang,et al. Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice[J]. THERANOSTICS,2024,14(14):5429-5442. |
| APA | Samarawickrama, Priyadarshani Nadeeshika.,Zhang, Guiqin.,Zhu, Enfang.,Dong, Xin.,Nisar, Ayesha.,...&He, Yonghan.(2024).Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice.THERANOSTICS,14(14),5429-5442. |
| MLA | Samarawickrama, Priyadarshani Nadeeshika,et al."Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice".THERANOSTICS 14.14(2024):5429-5442. |
入库方式： OAI收割
来源：上海药物研究所
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