Regulatory effect and mechanism of microRNA-146 in graft rejection after liver transplantation

doi:10.3877/cma.j.issn.2095-3232.2018.04.018

Abstract

Abstract:

Objective

To investigate the regulatory effect and mechanism of microRNA-146 (miR-146) in graft rejection after liver transplantation (LT).

Methods

Orthotopic LT models of two groups were established using two-cuff technique. In the allotransplantation model group (experimental group), Lewis rats were used as the donors and BN rats as the recipients. In the isotransplantation model group (control group), Lewis rats were used as both the donors and recipients, with 3 rats in each group. At 7 d after LT, liver tissues were collected for histopathological examination and microRNA high-throughput sequencing. The GO and KEGG signaling pathways of miR-146 target genes were analyzed using bioinformatics website.

Results

Histopathological examination revealed that the rejection activity index (RAI) of liver tissues in the experimental group was 8.4±0.5 and the rats were diagnosed with severe acute rejection. In the control group, the RAI was 1.5±0.5 and the rats were diagnosed with no graft rejection. High-throughput sequencing showed that among 22 microRNAs which were probably closely associated with graft rejection, the expression levels of 21 were significantly up-regulated in the experimental group compared with those in the control group. Two of the 21 up-regulated microRNAs, miR-146a-5P and miR-146b-5P, were members of miR-146 family, and their expression levels were respectively 1.1 and 2.3 times of those in the control group. GO and KEGG signaling pathway analysis revealed that miR-146a-5P and miR-146b-5P participated in multiple immune-related signaling pathways via the target genes interleukin-1 receptor-associated kinase 1 (IRAK1), nuclear factor of activated T-cells 5 (NFAT5) and tumor necrosis factor receptor-associated protein family 6 (TRAF6).

Conclusions

The up-regulated expression levels of miR-146a-5P and miR-146b-5P are correlated with the incidence of graft rejection in rat with allogeneic LT. The mechanism is probably mediating multiple immune-related signaling pathways through regulating the expression of IRAK1, NFAT5 and TRAF6.

Key words: MicroRNAs, Liver transplantation, Graft rejection, miR-146

Qiangxing Chen, Jian Zhang, Kun Li, Shuguang Zhu, Cuicui Xiao, Weihao Kong, Zenan Huang. Regulatory effect and mechanism of microRNA-146 in graft rejection after liver transplantation[J]. Chinese Journal of Hepatic Surgery(Electronic Edition), 2018, 07(04): 332-337.

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Figures/Tables 5

References 21

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microRNA_ID	所属家族	上调/下调	log2(倍数变化)
rno-let-7i-5p	let-7家族	上调	1.1
rno-miR-10b-5p	miR-10家族	下调	-1.2
rno-miR-128-3p	miR-128家族	上调	1.1
rno-miR-142-3p	miR-142家族	上调	2.4
rno-miR-142-5p	miR-142家族	上调	2.3
rno-miR-146a-5p	miR-146家族	上调	1.1
rno-miR-146b-5p	miR-146家族	上调	2.3
rno-miR-150-5p	miR-150家族	上调	1.9
rno-miR-155-5p	miR-155家族	上调	4.0
rno-miR-17-5p	miR-17家族	上调	1.5
rno-miR-106b-3p	miR-17家族	上调	1.2
rno-miR-181a-5p	miR-181家族	上调	1.2
rno-miR-181b-5p	miR-181家族	上调	1.8
rno-miR-221-3p	miR-221家族	上调	1.8
rno-miR-223-3p	miR-223家族	上调	1.5
rno-miR-23a-3p	miR-23家族	上调	1.1
rno-miR-27a-3p	miR-27家族	上调	1.0
rno-miR-27a-5p	miR-27家族	上调	1.2
rno-miR-342-3p	miR-342家族	上调	1.4
rno-miR-363-3p	miR-363家族	上调	3.0
rno-miR-425-5p	miR-425家族	上调	1.2
rno-miR-7a-5p	miR-7家族	上调	1.4

microRNA_ID	所属家族	上调/下调	log2(倍数变化)
rno-let-7i-5p	let-7家族	上调	1.1
rno-miR-10b-5p	miR-10家族	下调	-1.2
rno-miR-128-3p	miR-128家族	上调	1.1
rno-miR-142-3p	miR-142家族	上调	2.4
rno-miR-142-5p	miR-142家族	上调	2.3
rno-miR-146a-5p	miR-146家族	上调	1.1
rno-miR-146b-5p	miR-146家族	上调	2.3
rno-miR-150-5p	miR-150家族	上调	1.9
rno-miR-155-5p	miR-155家族	上调	4.0
rno-miR-17-5p	miR-17家族	上调	1.5
rno-miR-106b-3p	miR-17家族	上调	1.2
rno-miR-181a-5p	miR-181家族	上调	1.2
rno-miR-181b-5p	miR-181家族	上调	1.8
rno-miR-221-3p	miR-221家族	上调	1.8
rno-miR-223-3p	miR-223家族	上调	1.5
rno-miR-23a-3p	miR-23家族	上调	1.1
rno-miR-27a-3p	miR-27家族	上调	1.0
rno-miR-27a-5p	miR-27家族	上调	1.2
rno-miR-342-3p	miR-342家族	上调	1.4
rno-miR-363-3p	miR-363家族	上调	3.0
rno-miR-425-5p	miR-425家族	上调	1.2
rno-miR-7a-5p	miR-7家族	上调	1.4

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