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 a recent study was to identify the key exosomal miRNA that played vital roles in liver regeneration.

Sprague–Dawley male rats were assigned to a 70% partially hepatectomized group (n = 6) and a sham surgery group (n = 6). The peripheral blood of both groups was collected 24 h after surgery. The exosomal miRNAs were extracted, and miRNA 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. Western blotting was used to validate the predicted target of the key miRNA.

Exosomal miR-10a was found to be upregulated more than nine times in hepatectomized rats. The level of miR-10a was increased in the early phase of liver regeneration, reached the top at 72 h postsurgery, and decreased to perioperative level 168 h after surgery. Moreover, enforced expression of miR-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 EphA4 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.

From this evidence, researchers conclude that exosomal miR-10a might accelerate liver regeneration through downregulation of EphA4.

Identification of the exosomal key miRNA in liver regeneration

(a) Transmission electron microscopy of the exosomes extracted from the PB. (b) Western blot of exosome marker CD9 and CD63. (c) Microarray analysis results of key microRNA working in liver regeneration. (d) Quantitative polymerase chain reaction results of miR-10a levels in liver regeneration. PH: Partial hepatectomy; SH: Sham.


L. Luo, ZP Yu, H. Qin, ZX Zhu, MH Liao, HT Liao, KF Yuan, Y. Zeng (2018) Exosomal MicroRNA-10a Is Associated with Liver Regeneration in Rats through Downregulation of EphA4 Chinese Medical Journal doi: 10.4103/0366-6999.225057 [article]

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