HIV Tat Protein Induces Myocardial Fibrosis Through TGF-β1-CTGF Signaling Cascade: A Potential Mechanism of HIV Infection-Related Cardiac Manifestations
HIV Tat Protein Induces Myocardial Fibrosis Through TGF-β1-CTGF Signaling Cascade: A Potential Mechanism of HIV Infection-Related Cardiac Manifestations
复制标题
HIV Tat蛋白通过TGF-β1-CTGF信号级联诱导心肌纤维化：HIV感染相关心脏表现的潜在机制
DOI：
10.1007/s12012-021-09687-6
复制
发表时间：
2021-09-14
影响因子：
3.2
通讯作者：
Bai, Yunlong
中科院分区：
文献类型：
--
作者：
Jiang, Yannan;Chai, Lu;Bai, Yunlong
人类免疫缺陷病毒（HIV）感染是心血管疾病（cvd）的危险因素。hiv感染患者表现为心功能障碍并伴有心脏纤维化。然而，HIV能够诱导心脏纤维化的原因在很大程度上仍未被探索。HIV-1转录反式激活因子（Tat）蛋白是一种调节蛋白，在各种hiv相关并发症的发病机制中起关键作用。在本研究中，重组Tat以不同剂量给予小鼠心肌或新生小鼠心脏成纤维细胞。采用苏木精-伊红染色和马松三色染色观察小鼠心肌组织的组织学变化。采用EdU染色法和MTS法分别评价新生小鼠心脏成纤维细胞的增殖和活力。采用Real-time PCR和western blot分别检测CTGF、tgf - β 1和collagen I mRNA和蛋白的表达水平。结果表明，泰可促进小鼠心肌纤维化的发生。此外，我们发现Tat增加了新生小鼠心脏成纤维细胞的增殖能力和活力。tgf - β 1和CTGF蛋白和mRNA的表达水平在经tat处理的小鼠心肌和新生小鼠心脏成纤维细胞中均显著上调。然而，联合使用tgf - β抑制剂可消除Tat诱导的新生小鼠心脏成纤维细胞中胶原I的增强表达。总之，Tat通过增强tgf - β 1-CTGF信号级联参与hiv相关的心脏纤维化。
Human immunodeficiency virus (HIV) infection is a risk factor of cardiovascular diseases (CVDs). HIV-infected patients exhibit cardiac dysfunction coupled with cardiac fibrosis. However, the reason why HIV could induce cardiac fibrosis remains largely unexplored. HIV-1 trans-activator of transcription (Tat) protein is a regulatory protein, which plays a critical role in the pathogenesis of various HIV-related complications. In the present study, recombinant Tat was administered to mouse myocardium or neonatal mouse cardiac fibroblasts in different doses. Hematoxylin-eosin and Masson's trichrome staining were performed to observe the histological changes of mice myocardial tissues. EdU staining and MTS assay were used to evaluate the proliferation and viability of neonatal mouse cardiac fibroblasts, respectively. Real-time PCR and western blot analysis were used to detect CTGF, TGF-beta 1, and collagen I mRNA and protein expression levels, respectively. The results showed that Tat promoted the occurrence of myocardial fibrosis in mice. Also, we found that Tat increased the proliferative ability and the viability of neonatal mouse cardiac fibroblasts. The protein and mRNA expression levels of TGF-beta 1 and CTGF were significantly upregulated both in Tat-treated mouse myocardium and neonatal mouse cardiac fibroblasts. However, co-administration of TGF-beta inhibitor abrogated the enhanced expression of collagen I induced by Tat in neonatal mouse cardiac fibroblasts. In conclusion, Tat contributes to HIV-related cardiac fibrosis through enhanced TGF-beta 1-CTGF signaling cascade.