在多发性髓瘤细胞上,LILRB4通过p-SHP2/NF-κB/RELT信号通路促进骨损伤
Hongying Wang1, Lei Wang1, Huiwen Luan1
1Department of Biochemistry and Molecular Biology, Shandong Tumour Immunotherapy Research Innovation Team, Binzhou Medical University, Yantai, Shandong, 264003, P.R. China.
概括
白细胞Ig类受体B家族4 (LILRB4) 通过RELT增强骨质细胞分化,促进多发性骨髓瘤骨病变. 阻止LILRB4信号传递会抑制骨损伤,提供治疗点.
科学领域:
- 免疫学 免疫学 免疫学
- 在瘤学瘤学.
- 骨生物学 骨生物学 骨生物学
背景情况:
- 白细胞Ig类受体B家族4 (LILRB4) 是髓状细胞的免疫检查点,具有瘤治疗的潜力.
- 多发性骨髓瘤的特征是骨解性骨损伤,但LILRB4在这个过程中的作用尚不清楚.
研究的目的:
- 研究LILRB4在多发性骨髓瘤诱导的骨病变中的作用.
- 为了阐明LILRB4介导的骨损伤的潜在机制.
主要方法:
- 在多发性骨髓瘤样本和患者数据中分析LILRB4表达.
- 使用来自LILRB4-WT和-KO细胞的条件介质进行体外研究,以评估对骨质细胞和骨质母细胞的影响.
- 在体内研究使用异种移植,同源和患者衍生的异种移植模型来评估骨损伤.
- 分子分析包括RNA-seq,细胞因子阵列,qPCR,露西法酶测定,Co-IP和西式涂抹来确定机制.
主要成果:
- 在多发性骨髓瘤中,LILRB4的表达很高,与病变的严重程度相关.
- LILRB4促进骨质细胞分化和成熟,在体内调解骨损伤.
- RELT被确定为由LILRB4调节的关键细胞因子,能够再生骨损伤.
- 删除或阻断LILRB4,单独或与博尔特佐米布一起,显著延迟了骨损伤的进展.
结论:
- 通过RELT分泌,LILRB4通过增强骨质细胞分化和成熟来促进多发性骨髓瘤骨损伤.
- 阻止LILRB4信号通路是一种潜在的治疗策略,可以抑制多发性骨髓瘤中骨损伤的进展.
相关概念视频
NF-κB-dependent Signaling Pathway
7.4K
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...
NF-κB-dependent Signaling Mechanism
The...
7.4K
Abnormal Proliferation
4.5K
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...
4.5K


