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野百合碱诱导的肺动脉高压大鼠肥厚右心室中基质细胞蛋白的表达谱

Expression profile of matricellular proteins in hypertrophied right ventricle of monocrotaline-induced pulmonary hypertensive rats.

作者信息

Imoto Keisuke, Okada Muneyoshi, Yamawaki Hideyuki

机构信息

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35-1, Towada-shi, Aomori 034-8628, Japan.

出版信息

J Vet Med Sci. 2017 Jun 29;79(6):1096-1102. doi: 10.1292/jvms.17-0053. Epub 2017 May 11.

Abstract

Matricellular proteins, a non-structural extracellular matrix (ECM) component, bind to and modulate various molecules including growth factor, cytokine, protease, other ECM components and cell membrane receptors. While most matricellular proteins are hardly expressed in normal adult tissue, they are re-expressed in heart tissue during cardiac diseases. The present study aimed to clarify the mRNA expression profile of matricellular proteins [secreted protein acidic and rich in cysteine: SPARC, hevin, thrombospondin (TSP)-1, -2 and -4, CCN1 and 5, tenascin (Tn) C and N, periostin and osteopontin (OPN)] in hypertrophied right ventricle (RV) of monocrotaline (MCT)-induced pulmonary hypertensive rats. Male Wistar rats were intraperitoneally treated with MCT or saline. Two or three weeks after MCT treatment, echocardiography was performed, and mRNA expression of matricellular proteins was measured by real-time polymerase chain reaction. MCT (2 weeks) induced pulmonary hypertension, RV dysfunction and hypertrophy, which were all worsened 3 weeks after MCT treatment. Expression of mRNA for SPARC, hevin, TnC, TSP-1, -2 and -4, CCN1 and 5, periostin and OPN but not TnN was significantly upregulated in RV of MCT (2 weeks)-treated rats. Expression of mRNA for TSP-4, CCN1 and 5 and periostin was continuously increased in RV of MCT (3 weeks)-treated rats. The present study for the first time revealed the mRNA expression profile for matricellular proteins in RV of MCT-treated rats for 2 or 3 weeks, which will be helpful to clarify the relationship for matricellular proteins and pathogenesis of MCT-induced RV hypertrophy.

摘要

基质细胞蛋白是一种非结构性细胞外基质(ECM)成分,可与多种分子结合并对其进行调节,这些分子包括生长因子、细胞因子、蛋白酶、其他ECM成分和细胞膜受体。虽然大多数基质细胞蛋白在正常成年组织中几乎不表达,但在心脏疾病期间它们会在心脏组织中重新表达。本研究旨在阐明基质细胞蛋白[富含半胱氨酸的酸性分泌蛋白:SPARC、hevin、血小板反应蛋白(TSP)-1、-2和-4、CCN1和5、腱生蛋白(Tn)C和N、骨膜蛋白和骨桥蛋白(OPN)]在单氰胺(MCT)诱导的肺动脉高压大鼠肥厚右心室(RV)中的mRNA表达谱。雄性Wistar大鼠腹腔注射MCT或生理盐水。MCT治疗后两周或三周,进行超声心动图检查,并通过实时聚合酶链反应测量基质细胞蛋白的mRNA表达。MCT(2周)诱导肺动脉高压、RV功能障碍和肥厚,在MCT治疗3周后这些情况均恶化。在MCT(2周)治疗的大鼠RV中,SPARC、hevin、TnC、TSP-1、-2和-4、CCN1和5、骨膜蛋白和OPN的mRNA表达显著上调,但TnN的mRNA表达未上调。在MCT(3周)治疗的大鼠RV中,TSP-4、CCN1和5以及骨膜蛋白的mRNA表达持续增加。本研究首次揭示了MCT治疗2周或3周的大鼠RV中基质细胞蛋白的mRNA表达谱,这将有助于阐明基质细胞蛋白与MCT诱导的RV肥厚发病机制之间的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/59d8/5487790/1c5be85a87a7/jvms-79-1096-g001.jpg

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