Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression
Th17/Treg imbalance modulates rat myocardial fibrosis and heart failure by regulating LOX expression
复制标题
Th17/Treg失衡通过调节LOX表达调节大鼠心肌纤维化和心力衰竭
DOI：
10.1111/apha.13537
复制
发表时间：
2020-07-30
影响因子：
6.3
通讯作者：
Sun, Lin
中科院分区：
文献类型：
--
作者：
Lu, Min;Qin, Xinglei;Sun, Lin
Aim The imbalance of T helper (Th) 17/T regulatory (Treg) is involved in chronic heart failure (HF). The enzyme lysyl oxidase (LOX) contributes to myocardial fibrosis. This study was designed to decipher the regulatory mechanism of Th17/Treg on LOX expression and to validate whether Th17/Treg imbalance regulates myocardial fibrosis by modulating LOX expression. Methods Human cardiac fibroblasts (HCFs) were treated with angiotensin II (Ang II) and co-cultured with Th17 cells and Tregs which were polarized from control naive CD4(+)T cells. Th17 cells and Tregs were adoptively transferred into abdominal aortic coarctation-induced chronic HF rats to investigate the efficacy of Th17 and Treg infusions on myocardial fibrosis and HF. Results Th17/Treg imbalance (increased Th17 cells and decreased Tregs) was observed in HF patients. Th17 cells/Tregs aggravated/attenuated Ang II-induced upregulation of LOX and fibrosis-related indicators (MMP-2/9 and collagen I/III) in HCFs in vitro and abdominal aortic coarctation-induced myocardial fibrosis and HF in rats, by promoting/inhibiting LOX expression. Mechanistically, Th17 cells promoted LOX expression by activating the IL-17/ERK1/2-AP-1 pathway, while Tregs inhibited LOX expression by activating the IL-10/JAK1-STAT3 pathway. Conclusion Increased Th17 cells and decreased Tregs aggravate myocardial fibrosis and HF by inducing LOX expression.
