Background: MicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miR...Background: MicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration. Methods: The Sprague-Dawley male rats were assigned to 70% partially hepatectomized group (n = 6) and sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA) staining was applied to study the effect of key miRNA overexpression on liver regeneration. Westenl blotting was used to validate the predicted target of the key miRNA. Results: Exosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in tile early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression ofmiR- 10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein level of EpbA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle. Conclusion: Exosomal miR- 10a might accelerate liver regeneration through downregulation of EphA4.展开更多
INTRODUCTION In 2002, Cherqui et al. reported the first purely laparoscopic living-donor left lateral sectionectomy (LDLLS)Yl This technique has now become a standardized procedure and has significantly shortened do...INTRODUCTION In 2002, Cherqui et al. reported the first purely laparoscopic living-donor left lateral sectionectomy (LDLLS)Yl This technique has now become a standardized procedure and has significantly shortened donor hospitalization.lZl The da Vinci robotic surgical system was introduced into the field of liver surgery more than 10 years ago. Its flexible mechanical "wrist" and stable three-dimensional (3D) visual field help minimize risks from complicated procedures.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China (No. 81672882 and No. 81502441) and Science and Technology Support Program of Sichuan Province (No. 2017SZ0003).
文摘Background: MicroRNAs (miRNAs) have been reported to play vital roles in liver regeneration. Previous studies mainly focused on the functions of intracellular miRNAs, while the functions of circulating exosomal miRNAs in liver regeneration remain largely unknown. The aim of this study was to identify the key exosomal miRNA that played vital roles in liver regeneration. Methods: The Sprague-Dawley male rats were assigned to 70% partially hepatectomized group (n = 6) and sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and microarray was used to find out the key miRNA implicated in liver regeneration. Adenovirus was used to overexpress the key miRNA in rats, and proliferating cell nuclear antigen (PCNA) staining was applied to study the effect of key miRNA overexpression on liver regeneration. Westenl blotting was used to validate the predicted target of the key miRNA. Results: Exosomal miR-10a was upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in tile early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression ofmiR- 10a by adenovirus facilitated the process of liver regeneration as evidenced by immunohistochemical staining of PCNA. Erythropoietin-producing hepatocellular receptor A4 (EphA4) has been predicted to be a target of miR-10a. The protein level of EpbA4 was decreased in the early phase of liver regeneration, reached the bottom at 72 h postsurgery, and rose to perioperative level 168 h after surgery, which was negatively correlated with miR-10a, confirming that EphA4 served as a downstream target of miR-10a. Moreover, inhibition of EphA4 by rhynchophylline could promote the proliferation of hepatocytes by regulating the cell cycle. Conclusion: Exosomal miR- 10a might accelerate liver regeneration through downregulation of EphA4.
文摘INTRODUCTION In 2002, Cherqui et al. reported the first purely laparoscopic living-donor left lateral sectionectomy (LDLLS)Yl This technique has now become a standardized procedure and has significantly shortened donor hospitalization.lZl The da Vinci robotic surgical system was introduced into the field of liver surgery more than 10 years ago. Its flexible mechanical "wrist" and stable three-dimensional (3D) visual field help minimize risks from complicated procedures.