Mechanism underlying rat hepatocyte apoptosis regulated by exosomes derived from bone marrow mesenchymal stem cells

doi:10.12307/2023.916

Abstract

Abstract: BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can release a large number of exosomes (Exos). The effect of Exos derived from BMSCs on hepatocyte apoptosis and the specific mechanism has not been fully clarified.
OBJECTIVE: To explore the effect of miR-21-5p carried by Exos derived from BMSCs on apoptosis of rat liver cells and its mechanism.
METHODS: Rat BMSCs were isolated and miR-21-5p NC or miR-21-5p inhibitor was transfected into BMSCs. The Exos were extracted by ultracentrifugation and named (BMSCs+miR-21-5p NC)-Exos and (BMSCs+miR-21-5p inhibitor)-Exos. BMSCs-derived Exos were co-cultured with rat hepatocytes to observe the effect of inhibiting miR-21-5p expression on the apoptosis of rat hepatocytes. The targeting relationship between miR-21-5p and PIK3R1 was verified by double luciferase reporter gene detection. TUNEL was used to detect the effect of miR-21-5p directly targeting PIK3R1 in Exos to activate the PI3K/AKT signaling pathway on hepatocyte apoptosis in BRL rats.
RESULTS AND CONCLUSION: (1) The double luciferase reporting system confirmed that when PI3KR1 wild type vector and miR-21-5p mimics co-transfected 293T cells, the luciferase activity decreased significantly compared with the PI3KR1 mutant vector co-transfected group, indicating that miR-21-5p could target PIK3R1. (2) TUNEL test results showed that compared with (BMSCs+miR-21-5p NC)-Exos group, (BMSCs+miR-21-5p inhibitor)-Exos treatment significantly increased the apoptosis rate. Compared with the (BMSCs+miR-21-5p NC)-Exos group, after the addition of AKT inhibitor LY294002, the apoptosis rate was significantly increased. (3) The results indicate that Exos may inhibit the apoptosis of BRL rat hepatocytes through miR-21-5p, in which miR-21-5p directly targets PIK3R1 to activate PI3K/AKT signaling pathway.

Key words: bone marrow mesenchymal stem cell, exosome, miR-21-5p, hepatocyte, apoptosis, PIK3R1

CLC Number:

Zheng Rongjiong, Deng Zerun, Han Dan, Sun Lihua. Mechanism underlying rat hepatocyte apoptosis regulated by exosomes derived from bone marrow mesenchymal stem cells[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(1): 44-49.

Figures/Tables 6

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