Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression
Mesenchymal stem cell infusion therapy in a carbon tetrachloride-induced liver fibrosis model affects matrix metalloproteinase expression
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DOI：
10.1042/cbi20090386
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发表时间：
2010-06-01
影响因子：
3.9
通讯作者：
Baharvand, Hossein
中科院分区：
文献类型：
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作者：
Rabani, Vahideh;Shahsavani, Mansoureh;Baharvand, Hossein
为了研究骨髓来源的间充质干细胞（MSCs）在逆转肝纤维化中的作用，并确定其可能的作用机制，将小鼠MSCs输注到CCl4注射小鼠慢性模型的尾静脉中。移植后4周，MSCs引起肝纤维化的病理组织学减少。定量分析证实肝胶原蛋白减少。此外，CCl4/MSC组的脂质过氧化明显降低。定量RT（逆转录）-PCR分析显示，移植后4周，与0014组相比，CCl4/MSC组肝脏胶原蛋白表达降低，MMP13（基质金属蛋白酶13）表达升高，MSCs具有显著的抗纤维化作用。在CCl4/MSC组中，α - SMA（平滑肌肌动蛋白）和TIMP1的表达也下调。此外，ccl4处理组MMP9的表达显著上调；但注射MSC后无明显变化。移植细胞在受体肝脏中很少，并且能够分化为白蛋白阳性细胞。综上所述，MSCs可能通过影响MMPs的表达而减少胶原沉积，从而促进ccl4损伤小鼠肝脏的恢复。
In order to investigate the effects of bone marrow-derived MSCs (mesenchymal stem cells) in reversing liver fibrosis and to determine their possible mechanism of action, mouse MSCs were infused into the tail vein of a CCl4 injection mouse chronic model. MSCs caused a decrease in liver fibrosis histopathologically, 4 weeks after transplantation. The reduction in liver collagen was confirmed by quantitative analysis. Moreover, lipid peroxidation in the CCl4/MSC group decreased significantly. Quantitative RT (reverse transcription)-PCR analysis showed administration of MSCs has a significant antifibrotic effect as evidenced by the decrease in expression of liver collagen and increase in MMP13 (matrix metalloproteinase 1 3) in the CCl4/MSC group when compared with the 0014 group, 4 weeks after transplantation. The expression of alpha SMA (smooth muscle actin) and TIMP1 was also down-regulated in the CCl4/MSC group. Additionally, the expression of MMP9 was significantly up-regulated in the CCl4-treated group; however, there was no significant change after MSC injection. Few engrafted cells in the recipient liver and were able to differentiate into albumin-positive cells. In conclusion, MSCs can enhance recovery of a CCl4-injured mouse liver through their influence in reducing collagen deposition by possibly affecting expression of MMPs.