PDF(Pubmed)
Abstract：
Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF-/- C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF-/-; MIF-/-+Bet; TAA group, which received TAA; TAA+Bet; MIF-/-+TAA; and MIF-/-+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.
摘要：
巨噬细胞抑制因子(MIF)是一种多能细胞因子,参与感染或损伤的炎症反应。本研究探讨了MIF在肝纤维化中的作用以及甜菜碱对硫代乙酰胺（TAA）诱导的肝纤维化中MIF的调节作用。将野生型和敲除的MIF-/-C57BL/6小鼠分为以下组：对照组；Bet组，接受甜菜碱；MIF-/-；MIF-/-Bet；TAA组，其接受TAA;TAA+Bet;MIF-/-+TAA;和MIF-/-+TAA+Bet组。经过八周的治疗,收集肝组织进行进一步分析.结果显示，TAA治疗的MIF缺陷小鼠肝脏TGF-β1和PDGF-BB水平升高，以及与TAA处理的野生型小鼠相比的MMP-2、MMP-9和TIMP-1。然而,对TAA治疗的MIF缺陷小鼠施用甜菜碱降低了肝脏TGF-β1和PDGF-BB水平，也降低了MMP-2，MMP-9和TIMP-1的相对活性，尽管效果不如TAA治疗的小鼠没有MIF缺陷。此外，MIF的抗纤维化作用由MMP2/TIMP1和MMP9/TIMP1比率的增加证明。肝组织的组织学检查证实了肝纤维化因子水平的变化。总的来说,MIF的双重性质突出了其参与肝纤维化的进展。它的促氧化和促炎作用最初可能会加剧组织损伤和炎症，但它的抗纤维化活性表明了对纤维化发展的潜在保护作用。研究表明，甜菜碱调节MIF在TAA诱导的肝纤维化中的抗纤维化作用，通过降低TGF-β1，PDGF-BB，MMP-2，MMP-9，TIMP-1和ECM（Coll1和Coll3）在肝脏中的沉积。
