Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice
Depletion of Bone Marrow-Derived Fibrocytes Attenuates TAA-Induced Liver Fibrosis in Mice
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DOI：
10.3390/cells8101210
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发表时间：
2019-10-01
期刊：
影响因子：
6
通讯作者：
Roeb, Elke
中科院分区：
文献类型：
--
作者：
Hempel, Felix;Roderfeld, Martin;Roeb, Elke
骨髓源性纤维细胞是一种独特的细胞类型，具有间充质细胞和造血细胞的共同特征。Fc特异性地渗入受损肝脏，参与肝纤维化的形成。此外，Fc还发挥多种旁分泌功能，可能影响疾病的进展。然而，FC对肝纤维化的总体贡献仍不清楚。我们的目的是利用单纯疱疹病毒胸苷激酶(HSV-TK)/valganciclovir自杀基因策略来研究特异性Fc耗竭的影响。用硫代乙酰胺(TAA)灌胃诱导C57BL/6J小鼠肝纤维化。以肝脏羟脯氨酸含量为主要读数进行评估。HSV-TK模型能够使纤维细胞特异性耗竭。肝组织羟脯氨酸含量在纤维细胞消融术后显著降低(-7.8%；95%CI：0.7-14.8%；p=0.033)，表明纤维胶原沉积减少。较低的血清丙氨酸转氨酶水平(-20.9%；95%可信区间：0.4-36.9%；p=0.049)表明肝脏特异性细胞损伤减轻。然而，具体的行动模式仍有待确定。本研究证明了纤维细胞在慢性中毒性肝纤维化中的相关功能贡献，这与最近的报道相矛盾。我们的结果强调有必要深入研究纤维细胞的生物学，以了解它们在肝纤维化形成中的重要性。
Bone marrow-derived fibrocytes (FC) represent a unique cell type, sharing features of both mesenchymal and hematopoietic cells. FC were shown to specifically infiltrate the injured liver and participate in fibrogenesis. Moreover, FC exert a variety of paracrine functions, thus possibly influencing the disease progression. However, the overall contribution of FC to liver fibrosis remains unclear. We aimed to study the effect of a specific FC depletion, utilizing a herpes simplex virus thymidine kinase (HSV-TK)/Valganciclovir suicide gene strategy. Fibrosis was induced by oral thioacetamide (TAA) administration in C57BL/6J mice. Hepatic hydroxyproline content was assessed for the primary readout. The HSV-TK model enabled the specific depletion of fibrocytes. Hepatic hydroxyproline content was significantly reduced as a result of the fibrocyte ablation (-7.8%; 95% CI: 0.7-14.8%; p = 0.033), denoting a reduced deposition of fibrillar collagens. Lower serum alanine transaminase levels (-20.9%; 95% CI: 0.4-36.9%; p = 0.049) indicate a mitigation of liver-specific cellular damage. A detailed mode of action, however, remains yet to be identified. The present study demonstrates a relevant functional contribution of fibrocytes to chronic toxic liver fibrosis, contradicting recent reports. Our results emphasize the need to thoroughly study the biology of fibrocytes in order to understand their importance for hepatic fibrogenesis.