相关实验视频

Updated: Jun 16, 2025

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

针对TFAM下调调节介导的mtDNA-NLRP3通路抑制了TAM透和HCC进展

Jing Zhao^1,2,3, Mengmeng Cui^1,4, Xiaojuan Yao^1,4

¹Laboratory of Cancer Biomarkers and Liquid Biopsy, School of Pharmacy, Henan University, Kaifeng, 475000, Henan, China.

|June 14, 2025

概括

在肝癌 (HCC) 中降低调节的TFAM会导致线粒体DNA (mtDNA) 的压力,激活NLRP3炎症酶. 这促进了M2-TAM的透,推动了瘤的进展,并创造了一个免疫抑制的瘤微环境.

科学领域:

在瘤学瘤学.
免疫学免疫学免疫学
分子生物学分子生物学

背景情况:

瘤相关巨细胞 (TAMs) 驱动免疫抑制性瘤微环境,对于肝细胞癌 (HCC) 进展至关重要.
TFAM (线粒体转录因子A) 调节线粒体DNA (mtDNA) 并且在HCC中经常被下调,但其在TAM透中的作用尚不清楚.

研究的目的:

调查TFAM下调影响TAM透到HCC中的机制.
探索细胞质mtDNA压力和NLRP3炎症酶途径在这个过程中的作用.

主要方法:

在HCC组织中分析TFAM和CD163表达.
研究TFAM下调对细胞质mtDNA应激,NLRP3炎症酶激活和HCC细胞中细胞因子 (IL-18,IL-1β) 生产的影响.
利用DNase I和NLRP3对手来阻止mtDNA压力和炎症酶激活.
在 ортотоп性小鼠模型中评估TAM透和瘤进展.

主要成果:

在HCC中,TFAM表达减少,与CD163表达相关.
TFAM下调诱导细胞质mtDNA压力,激活NLRP3炎症体并增加IL-18和IL-1β,从而促进M2-TAM招募和两极分化.
抑制细胞质mtDNA或NLRP3炎症酶激活抑制了M2-TAM透.
阻断mtDNA-NLRP3通路减少了TAM透,并在体内抑制了HCC的进展.

结论:

在HCC中TFAM下调会诱导细胞质mtDNA应激,激活NLRP3炎症体.
这一途径促进M2-TAM透,导致免疫抑制性瘤微环境和HCC进展.
准mtDNA-NLRP3通路代表了HCC的潜在治疗策略.

更多相关视频

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Author Spotlight: Exploring the Role of FAM83A in Cervical Cancer

Published on: February 9, 2024

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Transfer of Manipulated Tumor-associated Neutrophils into Tumor-Bearing Mice to Study their Angiogenic Potential In Vivo

Published on: July 20, 2019

相关概念视频

NF-κB-dependent Signaling Pathway

NF-κB-dependent Signaling Pathway

The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The...

Abnormal Proliferation

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...