Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice

	Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice
	Samarawickrama, PN; Zhang, GQ; Zhu, EF; Dong, X; Nisar, A; Zhu, H; Ma, Y; Zhou, ZY; Yang, HL; Gui, L; Cao, M; Li, W; Chang, Y; Zi, MT; Cui, HL; Duan, ZP; Zhang, X; Li, W; He, YH
	2024
发表期刊	THERANOSTICS
ISSN	1838-7640
卷号	14 期号:14 页码:5429-5442
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.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14471
专题	科研部门_衰老调控与功能研究（何永捍）
推荐引用方式 GB/T 7714	Samarawickrama, PN,Zhang, GQ,Zhu, EF,et al. Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice[J]. THERANOSTICS,2024,14(14):5429-5442.
APA	Samarawickrama, PN.,Zhang, GQ.,Zhu, EF.,Dong, X.,Nisar, A.,...&He, YH.(2024).Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice.THERANOSTICS,14(14),5429-5442.
MLA	Samarawickrama, PN,et al."Clearance of senescent cells enhances skin wound healing in type 2 diabetic mice".THERANOSTICS 14.14(2024):5429-5442.

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