Xin'an Medicine Research Center, The First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), Wuhu, China.
Research Center of Integration of Traditional Chinese and Western Medicine, Wannan Medical College, Wuhu, China.
Front Immunol. 2022 Jan 17;12:795626. doi: 10.3389/fimmu.2021.795626. eCollection 2021.
Metabolic intervention is a novel anti-rheumatic approach. The glycolytic regulator NAMPT has been identified as a therapeutic target of rheumatoid arthritis (RA), while other metabolic regulators coordinating NAMPT to perpetuate inflammation are yet to be investigated. We continuously monitored and validated expression changes of and inflammatory indicators in peripheral while blood cells from rats with collagen-induced arthritis (CIA). Gene transcriptional profiles of and samples from identical CIA rats were compared by RNA-sequencing. Observed gene expression changes were validated in another batch of CIA rats, and typical metabolic regulators with persistent changes during inflammatory courses were further investigated in human subjects. According to expression differences of identified genes, RA patients were assigned into different subsets. Clinical manifestation and cytokine profiles among them were compared afterwards. overexpression typically occurred in CIA rats during early stages, when and started to be up-regulated. Among differentially expressed genes between and CIA rat samples, changes of , the only glycolytic enzyme identified were sustained in the aftermath of acute inflammation. Similar to , expression in RA patients was higher than general population, which was synchronized with increase in RFn as well as inflammatory monocytes-related cytokines like Eotaxin. Meanwhile, RANTES levels were relatively low when and were overexpressed. Reciprocal interactions between TPI1 and HIF-1α were observed. HIF-1α promoted expression, while TPI1 co-localized with HIF-1α in nucleus of inflammatory monocytes. In short, although NAMPT and TPI1 dominate different stages of CIA, they similarly provoke monocyte-mediated inflammation.
代谢干预是一种新的抗风湿方法。糖酵解调节剂 NAMPT 已被确定为类风湿关节炎（RA）的治疗靶点，而其他协调 NAMPT 以维持炎症的代谢调节剂仍有待研究。我们连续监测并验证了胶原诱导关节炎（CIA）大鼠外周血单个核细胞中 和炎症指标的表达变化。通过 RNA 测序比较了来自相同 CIA 大鼠的 和 样本的基因转录谱。在另一批 CIA 大鼠中验证了观察到的基因表达变化，并进一步在人类受试者中研究了在炎症过程中持续变化的典型代谢调节剂。根据鉴定基因的表达差异，将 RA 患者分为不同的亚组。随后比较了它们之间的临床表现和细胞因子谱。在 CIA 大鼠中， 通常在早期过度表达，此时 和 开始上调。在 和 CIA 大鼠样本之间差异表达的基因中，唯一鉴定出的糖酵解酶 的变化在急性炎症消退后仍持续存在。与 类似，RA 患者的 表达高于一般人群，这与 RFn 以及与炎性单核细胞相关的细胞因子（如 Eotaxin）的增加同步。同时，当 和 过度表达时，RANTES 水平相对较低。观察到 TPI1 和 HIF-1α 之间的相互作用。HIF-1α 促进 表达，而 TPI1 与 HIF-1α 在炎性单核细胞的核中共定位。简而言之，尽管 NAMPT 和 TPI1 主导 CIA 的不同阶段，但它们同样引发单核细胞介导的炎症。
