BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFβ signaling pathway
BMSCs attenuate hepatic fibrosis in autoimmune hepatitis through regulation of LMO7-AP1-TGFβ signaling pathway
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DOI：
10.26355/eurrev_202102_24870
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发表时间：
2021-01-01
影响因子：
3.3
通讯作者：
Chen, Y-P
中科院分区：
文献类型：
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作者：
Chen, Z-K;Chen, D-Z;Chen, Y-P
目的：在之前的一项研究中，我们报道了骨间充质干细胞（BMSCs）移植可显著减轻小鼠自身免疫性肝炎（AIH）模型的肝损伤。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的炎症和纤维化中起作用尚不清楚。本研究旨在探讨骨髓间充质干细胞移植对LMO7的影响以及LMO7在肝纤维化中的作用。材料与方法：成功建立s100诱导的小鼠AIH和lps诱导的肝细胞损伤模型。将3个剂量的骨髓间充质干细胞经尾静脉注入AIH小鼠。lps处理的AML12细胞与BMSCs体外共培养。小干扰（si） LMO7 RNA和T5224 （AP-1特异性抑制剂）被用来证明LMO7- ap1转化生长因子(TGF)- β之间的关系。结果：病理检查及血清丙氨酸和天冬氨酸转氨酶水平显示，骨髓间质干细胞处理小鼠肝损伤明显改善。经BMSCs干预后，LMO7水平上调，AP-1和tgf - β水平下调。与对照组相比，siLMO7组AP-1表达上调，而T5224组tgf - β水平下调。结论：BMSC移植可显著抑制肝纤维化，上调LMO7的表达。LMO7通过抑制AP-1抑制tgf - β通路。这意味着骨髓间充质干细胞是治疗肝纤维化的一种潜在手段。这种方法对AIH和其他纤维化疾病的治疗具有重要意义。
OBJECTIVE: 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.MATERIALS AND METHODS: 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)-beta.RESULTS: 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-beta levels were downregulated upon intervention with BMSCs. AP-1 expression was upregulated in the siLMO7 group, whereas TGF-beta level was down-regulated in the T5224 group when compared to those in the control group.CONCLUSIONS: BMSC transplantation significantly limits liver fibrosis and upregulates the expression of LMO7. LMO7 inhibits the TGF-beta 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.