miR-27b对血红素加氧酶1表达的调控与大鼠肝脏再生的干细胞治疗
Regulation of heme oxygenase 1 expression by miR-27b with stem cell therapy for liver regeneration in rats.
作者信息
Chen K-D, Hsu L-W, Goto S, Huang K-T, Nakano T, Weng W-T, Lai C-Y, Kuo Y-R, Chiu K-W, Wang C-C, Cheng Y-F, Lin C-C, Ma Y-Y, Chen C-L
机构信息
Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Center for Translational Research in Biomedical Sciences, Liver Transplantation Program, Graduate Institute of Clinical Medical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
出版信息
Transplant Proc. 2014 May;46(4):1198-200. doi: 10.1016/j.transproceed.2013.12.013.
Adipose-derived mesenchymal stem cells (ASCs) have been considered to be attractive and readily available adult mesenchymal stem cells (MSCs) and are becoming increasingly popular for use in regenerating cell therapy. However, recent evidence attributed a fibrotic potential to MSCs which differentiated into myofibroblasts with highly increased α-smooth muscle actin (α-SMA) expression while transplanted into an injured/regenerating liver in mice. In this study, we studied the role of miR-27b in ASCs and their regenerative potential after partial liver resection in rats. ASCs transfected with control siRNA or miR-27b were intravenously injected into autologous rats undergoing 70% partial hepatectomy (PH). Our data showed that the regenerative capacities of ASCs with overexpressed miR-27b were significantly higher compared with control ASCs. However, the enhanced regeneration, hepatic differentiation, and suppressed liver inflammation, as well as fibrotic activity, were significantly reverted by ZnPP coadministration (heme oxygenase-1 [HO-1] inhibitor) indicating an important role of HO-1 in the regenerating and cytoprotective activities of miR-27b-transfected ASCs. We demonstrated that administration of autologous ASCs overexpressed with miR-27b enhances rapid and early liver regeneration and, importantly, preserves function after PH. The ASCs with miR-27b overexpression might offer a viable therapeutic option to facilitate rapid recovery after liver resection.
脂肪来源的间充质干细胞（ASCs）被认为是有吸引力且易于获取的成人间充质干细胞（MSCs），并在再生细胞治疗中的应用越来越广泛。然而，最近有证据表明，MSCs具有纤维化潜能，在移植到小鼠受伤/再生的肝脏中时，会分化为α平滑肌肌动蛋白（α-SMA）表达显著增加的肌成纤维细胞。在本研究中，我们研究了miR-27b在大鼠部分肝切除术后ASCs中的作用及其再生潜能。将转染了对照siRNA或miR-27b的ASCs静脉注射到接受70%部分肝切除术（PH）的自体大鼠体内。我们的数据显示，与对照ASCs相比，miR-27b过表达的ASCs的再生能力显著更高。然而，锌原卟啉（血红素加氧酶-1 [HO-1]抑制剂）共同给药显著逆转了增强的再生、肝分化、抑制的肝脏炎症以及纤维化活性，表明HO-1在miR-27b转染的ASCs的再生和细胞保护活性中起重要作用。我们证明，给予miR-27b过表达的自体ASCs可增强肝脏的快速早期再生，重要的是，在部分肝切除术后保留肝功能。miR-27b过表达的ASCs可能为促进肝切除术后的快速恢复提供一种可行的治疗选择。
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