Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayis University, 55139, Kurupelit, Samsun, Turkey.
Department of Biochemistry, Faculty of Veterinary Medicine, Kırıkkale University, Kırıkkale, Turkey.
Cardiovasc Toxicol. 2018 Apr;18(2):142-160. doi: 10.1007/s12012-017-9426-y.
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4). The groups were further divided into three subgroups based on the duration of the experiment in which rats were killed on days 1, 7, and 28 (n = 7). Growth factors (VEGF, ANGPT, FGF-2, TGFβ), mitosis and apoptosis (Bcl-2, Bax, PCNA, Ki-67, phospho-histone H3), cell cycle activators and inhibitors (cyclin D1, D2, A2, Cdc2), the origin of regenerating cells (cKit and CD45) mRNA were detected using quantitative real-time polymerase chain reaction (PCR) and PCR array. Immunohistochemistry staining was used to directly detect protein level and distribution in the heart tissues. Administration of periostin following ISO-induced cardiotoxicity revealed that periostin alleviated deleterious effects of ISO through several pathways: (1) periostin induced mitotic activity of endothelial/fibroblastic cells, (2) periostin drives cardiomyocytes into S and M phases, thus promoting proliferation of cardiomyocytes, (3) periostin contributed to collagen degradation, tissue remodeling, and reduced cardiac fibrosis during the healing process following myocardial damage while preserving tissue matrix, (4) periostin stimulated angiogenesis by upregulating THBS1, TGFB2, and HGF genes, (5) periostin regulated cell growth and proliferation while maintaining cell shape and cellular muscle contractions (ACTB) and functioned as chemoattractant factor (CCL2) at the beginning of myocardial damage.
骨粘连蛋白是黏连蛋白家族的细胞外基质蛋白，在生物细胞黏附、迁移和生长中发挥重要作用。骨粘连蛋白可阻止细胞凋亡，同时刺激心肌细胞。本研究旨在探讨重组鼠骨粘连蛋白肽给药对异丙肾上腺素（ISO）诱导的心肌损伤大鼠模型的心脏保护作用。该实验在 84 只成年雄性 Sprague Dawley 大鼠（n=21）的 4 组中进行：对照组（1）、骨粘连蛋白处理组（2）、ISO 处理组（3）和 ISO+骨粘连蛋白处理组（4）。根据处死大鼠的时间（第 1、7 和 28 天）将每组进一步分为三个亚组（n=7）。使用定量实时聚合酶链反应（PCR）和 PCR 阵列检测生长因子（VEGF、ANGPT、FGF-2、TGFβ）、有丝分裂和细胞凋亡（Bcl-2、Bax、PCNA、Ki-67、磷酸化组蛋白 H3）、细胞周期激活剂和抑制剂（周期蛋白 D1、D2、A2、Cdc2）、再生细胞来源（cKit 和 CD45）的 mRNA。免疫组织化学染色用于直接检测心脏组织中的蛋白水平和分布。ISO 诱导的心脏毒性后给予骨粘连蛋白表明，骨粘连蛋白通过以下几种途径减轻 ISO 的有害作用：（1）骨粘连蛋白诱导内皮/成纤维细胞有丝分裂活性，（2）骨粘连蛋白将心肌细胞推向 S 和 M 期，从而促进心肌细胞增殖，（3）骨粘连蛋白有助于胶原蛋白降解、组织重塑和心肌损伤后愈合过程中的心脏纤维化减少，同时保留组织基质，（4）骨粘连蛋白通过上调 THBS1、TGFB2 和 HGF 基因刺激血管生成，（5）骨粘连蛋白调节细胞生长和增殖，同时保持细胞形状和细胞肌收缩（ACTB），并在心肌损伤开始时充当趋化因子（CCL2）。
