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应激反应基因 ankrd1a 在骨骼肌发育过程中是动态调节的,在成年斑马鱼心脏损伤的边缘区心肌细胞中上调。

The stress responsive gene ankrd1a is dynamically regulated during skeletal muscle development and upregulated following cardiac injury in border zone cardiomyocytes in adult zebrafish.

机构信息

Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biology, University of Belgrade, 11042 Belgrade, Serbia.

Max Planck Institute for Heart and Lung Research, Department of Developmental Genetics, 61231 Bad Nauheim, Germany.

出版信息

Gene. 2021 Aug 5;792:145725. doi: 10.1016/j.gene.2021.145725. Epub 2021 May 16.

DOI:10.1016/j.gene.2021.145725
PMID:34010705
Abstract

Ankyrin repeat domain 1 (ANKRD1) is a functionally pleiotropic protein found in the nuclei and sarcomeres of cardiac and skeletal muscles, with a proposed role in linking myofibrilar stress and transcriptional regulation. Rapid upregulation of its expression in response to both physiological and pathological stress supports the involvement of ANKRD1 in muscle tissue adaptation and remodeling. However, the exact role of ANKRD1 remains poorly understood. To begin to investigate its function at higher resolution, we have generated and characterized a TgBAC(ankrd1a:EGFP) zebrafish line. This reporter line displays transgene expression in slow skeletal muscle fibers during development and exercise responsiveness in adult cardiac muscle. To better understand the role of Ankrd1a in pathological conditions in adult zebrafish, we assessed ankrd1a expression after cardiac ventricle cryoinjury and observed localized upregulation in cardiomyocytes in the border zone. We show that this expression in injured hearts is recapitulated by the TgBAC(ankrd1a:EGFP) reporter. Our results identify novel expression domains of ankrd1a and suggest an important role for Ankrd1a in the early stress response and regeneration of cardiac tissue. This new reporter line will help decipher the role of Ankrd1a in striated muscle stress response, including after cardiac injury.

摘要

锚蛋白重复结构域 1(ANKRD1)是一种在心脏和骨骼肌的核和肌节中发现的功能多样的蛋白质,其在连接肌原纤维应激和转录调节方面具有一定作用。其表达在生理和病理应激下的快速上调,支持了 ANKRD1 参与肌肉组织适应和重塑。然而,ANKRD1 的确切作用仍知之甚少。为了更深入地研究其功能,我们构建并鉴定了一种 TgBAC(ankrd1a:EGFP)斑马鱼品系。该报告基因在斑马鱼发育过程中于慢肌纤维中表达,在成年心脏肌肉中有运动应答性。为了更好地了解 Ankrd1a 在成年斑马鱼病理条件下的作用,我们评估了心脏心室冷冻损伤后的 ankrd1a 表达,观察到在心肌细胞的边缘区有局部上调。我们表明,TgBAC(ankrd1a:EGFP)报告基因在受伤心脏中再现了这种表达。我们的结果确定了 ankrd1a 的新表达域,并提示 Ankrd1a 在心脏组织的早期应激反应和再生中具有重要作用。这种新的报告基因系将有助于解析 Ankrd1a 在横纹肌应激反应中的作用,包括心脏损伤后。

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