Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University, Zhejiang Provincial Key Laboratory for Accurate Diagnosis and Treatment of Chronic Liver.
Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1600-1611. doi: 10.26355/eurrev_202102_24870.
In a previous study, we reported that transplantation of bone mesenchymal stem cells (BMSCs) significantly attenuated liver damage in a mouse autoimmune hepatitis (AIH) model. Moreover, expression of the LIM domain protein, LMO7, correlated positively with the invasive capacity of hepatoma cells. However, whether LMO7 plays a role in inflammation and fibrosis of AIH remains unknown. This investigation aimed to explore the effect of BMSC transplantation on LMO7 and the role of LMO7 in hepatic fibrosis.
S100-induced murine AIH and LPS-induced hepatocyte injury models were successfully established. Three doses of BMSCs were injected into AIH mice via the tail vein. LPS-treated AML12 cells were co-cultured with BMSCs in vitro. Small interfering (si) LMO7 RNA and T5224 (a specific inhibitor of AP-1) were used to demonstrate the relationship between LMO7-AP1-transforming growth factor (TGF)-β.
Pathological examination and serum alanine and aspartate aminotransferase levels indicated that liver damage was notably ameliorated in the BMSC-treated mice. LMO7 level was upregulated, while AP-1 and TGF-β levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-β level was downregulated in the T5224 group when compared to those in the control group.
BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-β pathway by inhibiting AP-1. This implies that BMSCs are a potential means of treating liver fibrosis. This approach has important implications for the treatment of AIH and other fibrotic diseases.
在之前的研究中，我们报道了骨髓间充质干细胞（BMSCs）移植显著减轻了小鼠自身免疫性肝炎（AIH）模型中的肝损伤。此外，LIM 结构域蛋白 LMO7 的表达与肝癌细胞的侵袭能力呈正相关。然而，LMO7 是否在 AIH 的炎症和纤维化中发挥作用尚不清楚。本研究旨在探讨 BMSC 移植对 LMO7 的影响以及 LMO7 在肝纤维化中的作用。
成功建立了 S100 诱导的小鼠 AIH 和 LPS 诱导的肝细胞损伤模型。通过尾静脉向 AIH 小鼠注射三剂 BMSCs。体外将 LPS 处理的 AML12 细胞与 BMSCs 共培养。使用小干扰（si）LMO7 RNA 和 T5224（AP-1 的特异性抑制剂）来证明 LMO7-AP1-转化生长因子（TGF）-β之间的关系。
病理检查和血清丙氨酸转氨酶和天冬氨酸转氨酶水平表明，BMSC 治疗的小鼠肝损伤明显改善。干预后 LMO7 水平上调，而 AP-1 和 TGF-β水平下调。与对照组相比，siLMO7 组的 AP-1 表达上调，而 T5224 组的 TGF-β水平下调。
BMSC 移植显著限制肝纤维化并上调 LMO7 的表达。LMO7 通过抑制 AP-1 抑制 TGF-β 途径。这意味着 BMSCs 是治疗肝纤维化的一种潜在方法。这种方法对治疗 AIH 和其他纤维化疾病具有重要意义。
