Division of Neonatology, Batchelor Children Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
Department of Biochemistry, University of Illinois at Chicago, Chicago, Illinois.
Pediatr Res. 2017 Nov;82(5):863-871. doi: 10.1038/pr.2017.160. Epub 2017 Aug 2.
BackgroundCystein-rich protein 61 (Cyr61/CCN1) is a member of the CCN family of matricellular proteins that has an important role in tissue development and remodeling. However, the role of CCN1 in the pathogenesis of bronchopulmonary dysplasia (BPD) is unknown. Accordingly, we have investigated the effects of CCN1 on a hyperoxia-induced lung injury model in neonatal rats.MethodsIn experiment 1, newborn rats were randomized to room air (RA) or 85% oxygen (O) for 7 or 14 days, and we assessed the expression of CCN1. In experiment 2, rat pups were exposed to RA or O and received placebo or recombinant CCN1 by daily intraperitoneal injection for 10 days. The effects of CCN1 on hyperoxia-induced lung inflammation, alveolar and vascular development, vascular remodeling, and right ventricular hypertrophy (RVH) were observed.ResultsIn experiment 1, hyperoxia downregulated CCN1 expression. In experiment 2, treatment with recombinant CCN1 significantly decreased macrophage and neutrophil infiltration, reduced inflammasome activation, increased alveolar and vascular development, and reduced vascular remodeling and RVH in the hyperoxic animals.ConclusionThese results demonstrate that hyperoxia-induced lung injury is associated with downregulated basal CCN1 expression, and treatment with CCN1 can largely reverse hyperoxic injury.
背景
富含半胱氨酸蛋白 61（Cyr61/CCN1）是细胞外基质蛋白 CCN 家族的成员，在组织发育和重塑中具有重要作用。然而，CCN1 在支气管肺发育不良（BPD）发病机制中的作用尚不清楚。因此，我们研究了 CCN1 对新生大鼠高氧诱导肺损伤模型的影响。
方法
在实验 1 中，新生大鼠随机分为空气（RA）或 85%氧气（O）组，分别暴露 7 天或 14 天，评估 CCN1 的表达。在实验 2 中，大鼠暴露于 RA 或 O 中，并接受安慰剂或重组 CCN1 每日腹腔注射 10 天。观察 CCN1 对高氧诱导的肺炎症、肺泡和血管发育、血管重塑和右心室肥厚（RVH）的影响。
结果
在实验 1 中，高氧下调 CCN1 的表达。在实验 2 中，重组 CCN1 治疗显著减少了巨噬细胞和中性粒细胞浸润，降低了炎症小体的激活，增加了肺泡和血管的发育，减少了高氧动物的血管重塑和 RVH。
结论
这些结果表明，高氧诱导的肺损伤与基础 CCN1 表达下调有关，CCN1 治疗可显著逆转高氧损伤。
