Deficiency of SECTM1 impairs corneal wound healing in aging

IF 7.8 1区 医学 Q1 Biochemistry, Genetics and Molecular Biology Aging Cell Pub Date : 2024-06-17 DOI:10.1111/acel.14247
Jin Zhu, Xihong Lan, Kunlun Mo, Wang Zhang, Ying Huang, Jieying Tan, Li Wang, Jianping Ji, Qiong Ke, Hong Ouyang
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Abstract

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.

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缺乏 SECTM1 会影响衰老过程中角膜伤口的愈合。
角膜上皮是眼球最外层的透明屏障,在其生命周期中,角膜缘干细胞(LSCs)不断进行自我更新;然而,衰老对LSCs的影响在很大程度上仍然未知。在这里,我们发现老年猕猴(Macaca fascicularis)的角膜愈合能力明显低于年轻猕猴。伤口闭合延迟伴随着细胞排列紊乱和角膜混浊。研究发现,一种新型细胞因子--分泌和跨膜 1(SECTM1)--可促进角膜愈合,并在年轻猕猴伤口愈合时上调。从机制上讲,SECTM1 对 LSC 的迁移和增殖至关重要,并可能通过细胞分裂周期相关 7(CDCA7)发挥部分功能。值得注意的是,在老龄受伤角膜上局部应用 SECTM1 能显著促进小鼠和猕猴角膜的再上皮化并提高角膜透明度。我们的研究表明,衰老可能会损害非人灵长类动物角膜愈合反应因子的表达和损伤修复,在临床治疗中应用 SECTM1 有可能有利于角膜伤口愈合。
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来源期刊
Aging Cell
Aging Cell 生物-老年医学
CiteScore
14.40
自引率
2.60%
发文量
212
审稿时长
8 weeks
期刊介绍: Aging Cell, an Open Access journal, delves into fundamental aspects of aging biology. It comprehensively explores geroscience, emphasizing research on the mechanisms underlying the aging process and the connections between aging and age-related diseases.
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