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KIAA1429 通过促进血管瘤内皮细胞的干性来促进婴儿血管瘤的消退。

KIAA1429 promotes infantile hemangioma regression by facilitating the stemness of hemangioma endothelial cells.

机构信息

Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China.

Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

出版信息

Cancer Sci. 2023 Apr;114(4):1569-1581. doi: 10.1111/cas.15708. Epub 2023 Jan 10.

Abstract

Infantile hemangiomas are common vascular tumors with a specific natural history. The proliferation and regression mechanism of infantile hemangiomas may be related to the multilineage differentiation ability of hemangioma stem cells, but the specific mechanism is not well elucidated. KIAA1429 is an N -methyladenosine methylation-related protein that can also exert its role in a methylation-independent manner. This study aims to explore the function of KIAA1429 in infantile hemangiomas. qRT-PCR, western blotting, and immunostaining were performed to verify the expression of KIAA1429. The endothelial and fibroblast-like phenotypes of hemangioma endothelial cells were detected after KIAA1429 knockdown and overexpression. The stemness properties of hemangioma endothelial cells and the underlying mechanism of KIAA1429 in hemangiomas were also investigated. Nude mouse models of infantile hemangiomas were conducted to ascertain the effects of KIAA1429 in vivo. The results showed that KIAA1429 was highly expressed in infantile hemangiomas, particularly in involuting hemangiomas. In vitro experiments confirmed that KIAA1429 inhibited the endothelial phenotype, enhanced the differentiation ability, and promoted the fibroblast-like phenotype of hemangioma endothelial cells by inducing endothelial cell transition to facultative stem cells. However, the effect of KIAA1429 on the potential target was shown to be independent of N -methyladenosine methylation modification. Mouse models further revealed that KIAA1429 could inhibit the proliferation and promote the regression of hemangiomas. In conclusion, this study found that KIAA1429 played an important role in the regression of infantile hemangiomas by enhancing the stemness of hemangioma endothelial cells and could be a potential treatment target for infantile hemangiomas.

摘要

婴幼儿血管瘤是一种常见的血管肿瘤,具有特定的自然病史。婴幼儿血管瘤的增殖和消退机制可能与血管瘤干细胞的多谱系分化能力有关,但具体机制尚不清楚。KIAA1429 是一种 N-甲基腺苷甲基化相关蛋白,也可以以非甲基化依赖的方式发挥作用。本研究旨在探讨 KIAA1429 在婴幼儿血管瘤中的作用。采用 qRT-PCR、western blot 和免疫组化验证 KIAA1429 的表达。敲低和过表达 KIAA1429 后检测血管瘤内皮细胞的内皮和平滑肌样表型。还研究了血管瘤内皮细胞的干性特性和 KIAA1429 在血管瘤中的潜在作用机制。进行婴幼儿血管瘤裸鼠模型以确定 KIAA1429 在体内的作用。结果表明,KIAA1429 在婴幼儿血管瘤中高度表达,特别是在消退性血管瘤中。体外实验证实,KIAA1429 通过诱导内皮细胞向兼性干细胞转化,抑制内皮表型,增强血管瘤内皮细胞的分化能力,并促进其平滑肌样表型。然而,KIAA1429 对潜在靶标的作用被证明不依赖于 N-甲基腺苷甲基化修饰。小鼠模型进一步表明,KIAA1429 可抑制血管瘤的增殖并促进其消退。总之,本研究发现 KIAA1429 通过增强血管瘤内皮细胞的干性在婴幼儿血管瘤的消退中发挥重要作用,可能成为婴幼儿血管瘤的潜在治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa03/10067437/4ab630c297f5/CAS-114-1569-g001.jpg

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