淋巴管分泌信號促進心臟生長和修復
作者:
小柯機器人發布時間:2020/12/12 20:00:17
美國西北大學Guillermo Oliver研究小組發現,淋巴管分泌信號可促進心臟生長和修復。相關論文於2020年12月9日在線發表在《自然》雜誌上。
研究人員發現,淋巴管可以促進小鼠的心臟生長、修復和心臟保護。結果表明,由淋巴管內皮細胞(LEC)產生的淋巴管分泌信號控制心臟發育過程中心肌細胞的增殖和存活,改善新生兒心臟再生,並在心肌梗塞後具有心臟保護作用。缺乏LEC的胚胎會因心肌細胞增殖減少和心肌細胞凋亡增加而導致心臟變小。在LEC條件培養基中培養原代小鼠心肌細胞可增加心肌細胞的增殖和存活,這表明LEC產生控制心肌細胞穩態的淋巴血管分泌信號。LEC分泌基因組的鑑定表明細胞外蛋白reelin(RELN)是該過程的關鍵組成部分。
此外,研究人員發現,LEC特異性的Reln-null小鼠胚胎發育的心臟較小,RELN是新生兒心肌梗死後有效心臟修復和功能所必需的,並且使用膠原蛋白補丁對RELN進行心臟遞送可改善成年小鼠的心肌功能通過心臟保護作用。這些結果突出了LEC在心臟發育和損傷反應中的淋巴血管分泌作用,並確定RELN是該功能的重要介導因子。
據了解,最近的研究表明,淋巴管系統有助於心臟受傷後恢復心臟功能。
附:英文原文
Title: Lymphoangiocrine signals promote cardiac growth and repair
Author: Xiaolei Liu, Ester De la Cruz, Xiaowu Gu, Laszlo Balint, Michael Oxendine-Burns, Tamara Terrones, Wanshu Ma, Hui-Hsuan Kuo, Connor Lantz, Trisha Bansal, Edward Thorp, Paul Burridge, Zoltn Jakus, Joachim Herz, Ondine Cleaver, Miguel Torres, Guillermo Oliver
Issue&Volume: 2020-12-09
Abstract: Recent studies have suggested that lymphatics help to restore heart function after cardiac injury1,2,3,4,5,6. Here we report that lymphatics promote cardiac growth, repair and cardioprotection in mice. We show that a lymphoangiocrine signal produced by lymphatic endothelial cells (LECs) controls the proliferation and survival of cardiomyocytes during heart development, improves neonatal cardiac regeneration and is cardioprotective after myocardial infarction. Embryos that lack LECs develop smaller hearts as a consequence of reduced cardiomyocyte proliferation and increased cardiomyocyte apoptosis. Culturing primary mouse cardiomyocytes in LEC-conditioned medium increases cardiomyocyte proliferation and survival, which indicates that LECs produce lymphoangiocrine signals that control cardiomyocyte homeostasis. Characterization of the LEC secretome identified the extracellular protein reelin (RELN) as a key component of this process. Moreover, we report that LEC-specific Reln-null mouse embryos develop smaller hearts, that RELN is required for efficient heart repair and function after neonatal myocardial infarction, and that cardiac delivery of RELN using collagen patches improves heart function in adult mice after myocardial infarction by a cardioprotective effect. These results highlight a lymphoangiocrine role of LECs during cardiac development and injury response, and identify RELN as an important mediator of this function.
DOI: 10.1038/s41586-020-2998-x
Source: https://www.nature.com/articles/s41586-020-2998-x