Takai Yuichi, Watanabe Takeshi, Sano Tomoya
Drug Safety Research and Evaluation, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2 Chome, Fujisawa, Kanagawa 251-8555, Japan.
J Toxicol Pathol. 2022 Apr;35(2):183-192. doi: 10.1293/tox.2021-0061. Epub 2021 Dec 24.
The alteration in microRNA-210 level, a hypoxia-inducible microRNA, is not well known in non-ischemic tissue injury. In this study, we characterized the histopathological time course of acetic acid-induced skeletal muscle injury as a non-ischemic tissue injury model and investigated the expression of microRNA-210, hypoxia-inducible factor 1α, and growth factors using quantitative polymerase chain reaction analysis. After a single intramuscular dose of 3% (v/v) acetic acid to C57BL/6J mice, focal coagulative necrosis of muscle fibers was noted from 3 h after dosing and infiltration of F4/80 and Galectin-3 positive M2 macrophage was noted at 1 d after dosing. Muscular regeneration was initiated from 3 d, when M2 macrophage infiltration was most prominent, till 14 d after dosing. and expression increased from 3 h onwards, and microRNA-210 level increased after 3 d after the treatment. However, no clear elevation in the levels of or was observed. The infiltrative macrophages and regenerative muscle fibers were positive for hypoxia-inducible factor 1α, microRNA-210, and hepatocyte growth factor as assessed by immunohistochemistry or hybridization. In this study, dominant infiltration of M2 macrophages at muscular necrosis and subsequent regeneration after a single intramuscular injection of acetic acid in mice were observed. The increase in hif1α level was observed just after the muscular injury in this non-ischemic tissue injury model, and the elevation in microRNA-210 level was noted at the initiation of tissue regeneration, indicating its effects on tissue protection and repair.
微小RNA-210是一种缺氧诱导的微小RNA，其在非缺血性组织损伤中的变化尚不明确。在本研究中，我们将醋酸诱导的骨骼肌损伤作为非缺血性组织损伤模型，对其组织病理学时间进程进行了表征，并使用定量聚合酶链反应分析研究了微小RNA-210、缺氧诱导因子1α和生长因子的表达。给C57BL/6J小鼠单次肌内注射3%（v/v）醋酸后，给药后3小时即观察到肌纤维局灶性凝固性坏死，给药后1天观察到F4/80和半乳糖凝集素-3阳性M2巨噬细胞浸润。从给药后3天开始启动肌肉再生，此时M2巨噬细胞浸润最为明显，直至给药后14天。 和 的表达从3小时起增加，治疗后3天微小RNA-210水平升高。然而，未观察到 或 水平的明显升高。通过免疫组织化学或 杂交评估，浸润的巨噬细胞和再生的肌纤维对缺氧诱导因子1α、微小RNA-210和肝细胞生长因子呈阳性。在本研究中，观察到单次肌内注射醋酸后小鼠肌肉坏死时M2巨噬细胞的优势浸润以及随后的再生。在这个非缺血性组织损伤模型中，肌肉损伤后立即观察到hif1α水平升高，在组织再生开始时注意到微小RNA-210水平升高，表明其对组织保护和修复的作用。
