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细胞焦亡作为一把双刃剑:在炎症性疾病和癌症中的致病及治疗作用

Pyroptosis as a double-edged sword: The pathogenic and therapeutic roles in inflammatory diseases and cancers.

作者信息

Liu Zuohao, Wang Chunming, Lin Changjun

机构信息

School of Life Sciences, Lanzhou University, Lanzhou, China.

School of Life Sciences, Lanzhou University, Lanzhou, China.

出版信息

Life Sci. 2023 Apr 1;318:121498. doi: 10.1016/j.lfs.2023.121498. Epub 2023 Feb 11.

Abstract

Pyroptosis is a programmed cell death mode discovered in recent years. It is caused by inflammasomes and the perforation of Gasdermin family proteins, and results in the release of inflammatory factors and triggering of an inflammatory cascade response. The pathways of pyroptosis include the caspase-1-dependent canonical pathway, the caspase-4/5/11-dependent non-canonical pathway, other caspase-dependent pathways and caspase-independent pathways. Its morphological features are different from other programmed cell death modes (apoptosis, autophagy, etc.). Pyroptosis can be observed microscopically that abundant pores are formed in the cell membrane, resulting in cell swelling and rupture, and eventually leading to the outflow of cellular contents. In addition to causing tissue damage and dysfunction through inflammation, pyroptosis can also become a potential cancer treatment strategy by reducing drug resistance in cancer cells. However, many details are still unclear on the molecular mechanisms of its role in pathogenicity and therapeutics, and therefore lots of work needs to be done. This article reviews the morphological characteristics, pathogenic and therapeutic mechanisms of pyroptosis and its related research progress in inflammatory diseases and cancers. It helps to further understand the mechanism of pyroptosis and provide new ideas for the research and prevention of inflammatory diseases and cancers.

摘要

细胞焦亡是近年来发现的一种程序性细胞死亡模式。它由炎性小体和Gasdermin家族蛋白穿孔引起,导致炎性因子释放并引发炎症级联反应。细胞焦亡途径包括半胱天冬酶-1依赖的经典途径、半胱天冬酶-4/5/11依赖的非经典途径、其他半胱天冬酶依赖途径和半胱天冬酶非依赖途径。其形态学特征不同于其他程序性细胞死亡模式(凋亡、自噬等)。在显微镜下可观察到细胞焦亡时细胞膜上形成大量孔洞,导致细胞肿胀破裂,最终致使细胞内容物外流。细胞焦亡除了通过炎症导致组织损伤和功能障碍外,还可通过降低癌细胞耐药性成为一种潜在的癌症治疗策略。然而,其在致病性和治疗方面作用的分子机制仍有许多细节尚不清楚,因此仍需开展大量工作。本文综述了细胞焦亡的形态学特征、致病及治疗机制及其在炎症性疾病和癌症中的相关研究进展。有助于进一步了解细胞焦亡机制,为炎症性疾病和癌症的研究及防治提供新思路。

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