Department of Intensive Care Unit, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, PR China.
Lingnan Medical Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, Guangdong Province, PR China.
Cytokine. 2021 Jul;143:155509. doi: 10.1016/j.cyto.2021.155509. Epub 2021 Apr 9.
LncRNA PVT1 was reported to be elevated in septic myocardial tissue. The underlying mechanism by which PVT1 aggravated sepsis induced myocardial injury needs further investigation.
Mice was subjected to LPS injection to mimic in vivo sepsis model. HE staining was applied to observe tissue injury. Cardiac function of mice was determined by echocardiography. Bone marrow derived macrophage (BMDM) was used to confirm the regulatory effect of PVT1 in macrophage polarization. Western blotting or qRT-PCR were performed to evaluate protein or mRNA levels, respectively. ELISA was conducted to determine cytokine levels. Interaction between PVT1 and miR-29a, miR-29a and HMGB1 were accessed by dual luciferase assay.
Expression of PVT1 was elevated in myocardial tissue and heart infiltrating macrophages of sepsis mice. PVT1 knockdown alleviated LPS induced myocardial injury and attenuated M1 macrophage polarization. The mechanic study suggested that PVT1 targeted miR-29a, thus elevated expression of HMGB1, which was repressed by miR-29a targeting. The effect of PVT1 on M1 macrophage polarization was dependent on targeting miR-29a.
PVT1 promoted M1 polarization and aggravated LPS induced myocardial injury via miR-29a/HMGB1 axis.
已有研究报道长链非编码 RNA PVT1 在脓毒症心肌组织中表达升高。但 PVT1 加剧脓毒症诱导的心肌损伤的潜在机制仍需进一步研究。
采用 LPS 注射建立小鼠脓毒症模型，HE 染色观察组织损伤，超声心动图检测小鼠心功能，骨髓来源的巨噬细胞（BMDM）用于验证 PVT1 在巨噬细胞极化中的调控作用，Western blot 或 qRT-PCR 分别用于评估蛋白和 mRNA 水平，ELISA 用于检测细胞因子水平。双荧光素酶报告实验检测 PVT1 与 miR-29a、miR-29a 与 HMGB1 之间的相互作用。
脓毒症小鼠心肌组织和心脏浸润巨噬细胞中 PVT1 表达升高。PVT1 敲低可减轻 LPS 诱导的心肌损伤，并减弱 M1 型巨噬细胞极化。机制研究表明，PVT1 靶向 miR-29a，从而上调 HMGB1 的表达，而 miR-29a 靶向抑制 HMGB1 的表达。PVT1 对 M1 型巨噬细胞极化的影响依赖于对 miR-29a 的靶向作用。
PVT1 通过 miR-29a/HMGB1 轴促进 M1 极化并加重 LPS 诱导的心肌损伤。
