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伤口修复中的细胞衰老:针对慢性愈合伤口的新兴策略

Senescence in Wound Repair: Emerging Strategies to Target Chronic Healing Wounds.

作者信息

Wilkinson Holly N, Hardman Matthew J

机构信息

Centre for Atherothrombosis and Metabolic Disease, Hull York Medical School, University of Hull, Hull, United Kingdom.

出版信息

Front Cell Dev Biol. 2020 Aug 11;8:773. doi: 10.3389/fcell.2020.00773. eCollection 2020.

Abstract

Cellular senescence is a fundamental stress response that restrains tumour formation. Yet, senescence cells are also present in non-cancerous states, accumulating exponentially with chronological age and contributing to age- and diabetes-related cellular dysfunction. The identification of hypersecretory and phagocytic behaviours in cells that were once believed to be non-functional has led to a recent explosion of senescence research. Here we discuss the profound, and often opposing, roles identified for short-lived vs. chronic tissue senescence. Transiently induced senescence is required for development, regeneration and acute wound repair, while chronic senescence is widely implicated in tissue pathology. We recently demonstrated that sustained senescence contributes to impaired diabetic healing via the CXCR2 receptor, which when blocked promotes repair. Further studies have highlighted the beneficial effects of targeting a range of senescence-linked processes to fight disease. Collectively, these findings hold promise for developing clinically viable strategies to tackle senescence in chronic wounds and other cutaneous pathologies.

摘要

细胞衰老作为一种基本的应激反应,可抑制肿瘤形成。然而,衰老细胞也存在于非癌状态,随着自然年龄的增长呈指数级积累,并导致与年龄和糖尿病相关的细胞功能障碍。在曾经被认为无功能的细胞中发现了高分泌和吞噬行为,这引发了近期衰老研究的激增。在此,我们讨论了针对短期与慢性组织衰老所确定的深刻且往往相反的作用。短暂诱导的衰老对于发育、再生和急性伤口修复是必需的,而慢性衰老则广泛涉及组织病理学。我们最近证明,持续的衰老通过CXCR2受体导致糖尿病愈合受损,而阻断该受体可促进修复。进一步的研究强调了针对一系列与衰老相关的过程来对抗疾病的有益效果。总的来说,这些发现为开发临床上可行的策略以解决慢性伤口和其他皮肤病理中的衰老问题带来了希望。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea4c/7431694/47c0676a056e/fcell-08-00773-g001.jpg

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