Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice
Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice
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DOI：
10.1007/s00441-006-0334-x
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发表时间：
2007-03-01
影响因子：
3.6
通讯作者：
Sakaida, Isao
中科院分区：
文献类型：
--
作者：
Ishikawa, Tsuyoshi;Terai, Shuji;Sakaida, Isao
我们之前报道过成纤维细胞生长因子2 （FGF2）促进移植骨髓细胞（BMCs）分化为肝细胞。我们早期的研究还表明，FGF2联合骨髓移植（BMT）可协同激活肿瘤坏死因子- α信号，显著改善肝功能和预后。然而，其影响细胞外基质的方式尚不清楚。在这里，我们研究了FGF2联合BMT对四氯化碳（CCl4）处理小鼠肝纤维化的影响。与仅使用FGF2或单独使用BMT相比，bmc移植并同时使用FGF2治疗可显著降低ccl4诱导的肝纤维化，并伴有基质金属蛋白酶9的强表达。在此过程中，骨髓源性细胞的增殖速度加快，但不引起细胞凋亡。因此，FGF2联合BMT可协同改善ccl4诱导的小鼠肝纤维化。这种治疗方法有可能成为肝硬化患者的有效治疗方法。
We previously reported that fibroblast growth factor 2 (FGF2) facilitated the differentiation of transplanted bone marrow cells (BMCs) into hepatocytes. Our earlier study also demonstrated that administration of FGF2 in combination with bone marrow transplantation (BMT) synergistically activated tumor necrosis factor-alpha signaling and significantly improved liver function and prognosis more than BMT alone. However, the way that it affected the extracellular matrix remained unclear. Here, we investigated the effect of FGF2 treatment together with BMT on liver fibrosis in mice treated with carbon tetrachloride (CCl4). Transplantation of BMCs and concurrent treatment with FGF2 caused a statistically significant reduction in CCl4-induced liver fibrosis that was accompanied by strong expression of matrix metalloproteinase 9 as compared with FGF2-only treatment or BMT alone. Moreover, in this process, the proliferation of bone-marrow-derived cells was accelerated without causing apoptosis. Thus, the administration of FGF2 in combination with BMT synergistically improves CCl4-induced liver fibrosis in mice. This treatment has the potential of being an effective therapy for patients with liver cirrhosis.