RPL36-mediated selective loading of miR-4432 into extracellular vesicles contributes to perivascular cell dysfunction in venous malformations.

IF 11 1区 医学 Q1 DERMATOLOGY British Journal of Dermatology Pub Date : 2024-12-19 DOI:10.1093/bjd/ljae492
Gao-Hong Chen, Jian-Gang Ren, Hou-Fu Xia, He-Jing Zhang, Kui-Ming Wang, Lin-Zhou Zhang, Gang Chen
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引用次数: 0

Abstract

Background: Venous malformations (VMs), predominantly arising from activating mutations of tyrosine kinase receptor TIE2 within endothelial cells (ECs), are characterized by dilated and tortuous vessels with a paucity of perivascular cells. The mechanisms of interaction between mutant ECs and perivascular cells remain largely elusive.

Objectives: To investigate the characteristics of extracellular vesicles (EVs) from VM ECs, especially their carried miRNAs and their roles in the crosstalk between ECs and perivascular cells in VM pathogenesis.

Methods: MiRNA profiles of human umbilical vein endothelial cells overexpressing TIE2L914F (L914F cells) and TIE2WT (WT cells) along with their EVs were analyzed using RNA sequencing. In vitro studies using umbilical cord stem cells (UCSCs) were performed for the functional assays of VM EVs and their enriched microRNA-4432 (miR-4432). MiRNA-pulldown and RNA interference techniques were employed to identify the sorting regulator of miR-4432 into VM EVs.

Results: We observed an upregulation of RNA secretion in L914F EVs compared to WT EVs. MiRNA sequencing revealed a distinguished profile of L914F EVs compared to L914F cells, WT cells, and WT EVs, identifying miR-4432 as preferentially encapsulated within EVs from L914F cells. Functional assays demonstrated that VM EVs and EV-carried miR-4432 inhibited the differentiation, adhesion, and proliferation of UCSCs. Furthermore, RPL36 was identified as an RNA binding protein and sorting regulator of miR-4432 during the EV secretion process in L914F cells.

Conclusions: This study, for the first time, identifies the interaction between VM ECs and perivascular cells via EVs, and offers valuable data on the miRNA profiles of VM ECs and normal ECs, along with their EVs. Our findings suggest that the RPL36-mediated selective loading of miR-4432 into EVs may contribute to the aberrant perivascular cell coverage in VMs, providing novel insights into VM pathogenesis and potential treatment strategies.

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来源期刊
British Journal of Dermatology
British Journal of Dermatology 医学-皮肤病学
CiteScore
16.30
自引率
3.90%
发文量
1062
审稿时长
2-4 weeks
期刊介绍: The British Journal of Dermatology (BJD) is committed to publishing the highest quality dermatological research. Through its publications, the journal seeks to advance the understanding, management, and treatment of skin diseases, ultimately aiming to improve patient outcomes.
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Changes in skin research funding: the emergence of environmental sustainability criteria in the research competition assessment process. Barber Ant Alopecia. Bilateral periorbital leukemia cutis. Naevoid hyperkeratosis of the nipple and/or areola. RPL36-mediated selective loading of miR-4432 into extracellular vesicles contributes to perivascular cell dysfunction in venous malformations.
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