成纤维细胞通过增加COX4I2的表达介导嗜铬细胞瘤的血管生成。
Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression.
作者信息
Mao Yongxin, Zhuo Ran, Ma Wenming, Dai Jun, Alimu Parehe, Fang Chen, Xu Danfeng, Ye Lei, Wang Weiqing, Sun Fukang
机构信息
Department of Urology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.
出版信息
Front Oncol. 2022 Sep 12;12:938123. doi: 10.3389/fonc.2022.938123. eCollection 2022.
OBJECTIVE
Our previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma.
METHODS
Distribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells.
RESULTS
The scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF.
CONCLUSIONS
Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.
目的
我们之前的研究发现COX4I2与嗜铬细胞瘤的血管生成有关。本研究旨在探讨COX4I2在调节嗜铬细胞瘤血管生成中的作用。
方法
通过单细胞RNA测序（scRNA-seq）评估1例嗜铬细胞瘤中COX4I2的分布情况，并通过免疫染色进行验证。进一步在靶细胞中敲低COX4I2。通过qPCR评估靶细胞中血管生成相关基因的变化。
结果
scRNA-seq显示COX4I2在成纤维细胞中mRNA表达较高，而在肿瘤细胞中较低。COX4I2的免疫染色证实了其在成纤维细胞中的分布。在NIH3T3细胞系中敲低COX4I2导致血管生成相关基因显著减少，尤其是ANG1和HGF。
结论
成纤维细胞可能通过影响ANG1和HGF增加COX4I2的表达，从而介导嗜铬细胞瘤的血管生成。
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