Dataset Information

Loss of miR-673-5p expression in the cornea promotes rat corneal allograft rejection by promoting Th17 cell differentiation mediated by JAK2/STAT3.

ABSTRACT:

Background

Cluster of differentiation 4 positive (CD4⁺) T cells play an important role in corneal graft rejection, especially the dynamic balance between regulatory T cells and helper T cells. This study aims to explore the upstream and downstream regulatory mechanisms of Th17 cell differentiation-mediated corneal allograft rejection.

Methods

By establishing rat corneal allograft transplantation model, transcriptome analysis was carried out to screen the differentially expressed genes related to T helper 17 (Th17) cell differentiation, and then cell experiments were used to verify the effect of miR-673-5p/Janus Kinase 2 (JAK2) signal on naïve CD4⁺ T cell differentiation and the proliferation, migration, and tube formation ability of human umbilical vein endothelial cells (HUVECs). Finally, the role of miR-673-5p/JAK2 signal in corneal allograft rejection was verified by animal model in vivo.

Results

The results showed that JAK2/STAT3 signaling activation-mediated Th17 cell differentiation was significantly up-regulated during corneal allograft rejection, and miR-673-5p expression was down-regulated after corneal allograft rejection. Low expression of miR-673-5p promoted Th17 cell differentiation by up-regulating JAK2, and then promoted placental growth factor (PLGF)mediated corneal neovascularization (CNV).

Conclusions

The results of this study suggested that low expression of miR-673-5p is a promoter of corneal allograft rejection. Overexpression of miR-673-5p can improve the survival rate of corneal allografts by inhibiting the differentiation and maturation of Th17 cells mediated by JAK2/STAT3 signaling.

SUBMITTER: Cao Q

PROVIDER: S-EPMC8506749 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Publications

Loss of miR-673-5p expression in the cornea promotes rat corneal allograft rejection by promoting Th17 cell differentiation mediated by JAK2/STAT3.

Cao Qian Q Li Yunchuan Y Li Yong Y Li Lan L

Annals of translational medicine 20210901 18

<h4>Background</h4>Cluster of differentiation 4 positive (CD4<sup>+</sup>) T cells play an important role in corneal graft rejection, especially the dynamic balance between regulatory T cells and helper T cells. This study aims to explore the upstream and downstream regulatory mechanisms of Th17 cell differentiation-mediated corneal allograft rejection.<h4>Methods</h4>By establishing rat corneal allograft transplantation model, transcriptome analysis was carried out to screen the differentially ...[more]

PMID: 34733961

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Project description:BackgroundWorldwide, corneal transplantation (CT) is the most common type of tissue replacement and the increased rate of corneal graft rejection (CGR) after CT is a critical problem. Corneal endothelium cells (CECs) are often targets of the immune response mediated by graft-attacking effector T cells. However, the molecular mechanism underlying CGR remains poorly understood.MethodsThe differentially expressed microRNAs (miRNAs) and mRNA of graft-fail corneas were measured by transcriptome sequencing (RNA-Seq). real-time quantitative polymerase chain reaction was used to measure gene expression levels. Western blot and immunofluorescence staining were used to measure protein expression levels. Kaplan-Meier survival curves were constructed to assess corneal graft survival. Hematoxylin and eosin staining was used for histopathological examination. CCK-8 and ELISA staining were used to detect cell viability and inflammatory cytokines levels, respectively. Flow cytometry was used to detect cell apoptosis and the population of Treg and Th17. Transwell migration and wound-healing assays were used to measure cell migration.ResultsWe identified 453 miRNAs and 4,279 mRNAs aberrant expression in the corneas showing CGR. The differentially expressed miR-151-5p and its potential target gene [interleukin 2 receptor subunit alpha (IL-2Rɑ)] were selected from the RNA-Seq microarrays. The levels of miR-151-5p and IL-2Rɑ were respectively downregulated and upregulated in the CGR. The luciferase activity assay suggested that IL-2Rɑ is a target of miR-151-5p in 293 T cells. In addition, the miR-151-5p inhibitor, si-IL-2Rɑ, and oe-IL-2Rɑ transfection tests in CECs further confirmed that miR-151-5p downregulation and IL-2Rɑ overexpression promoted apoptosis of CECs and inhibited CEC migration, tight junction-related protein ZO-1 and Claudin-5 expression, and PI3K/AKT signaling pathway activity; however, downregulation of IL-2Rɑ abolished the inhibitor effect of miR-151-5p. Similarly, upregulation of miR-151-5p alleviated CGR via activation of the PI3K/AKT signaling pathway and balancing of Th17/Treg, and upregulation of IL-2Rɑ abolished the alleviating effect of miR-151-5p.ConclusionsUpregulation of miR-151-5p alleviated CGR by activating the PI3K/AKT signaling pathway and balancing Th17/Treg via targeting of IL-2Rɑ, which contributes to improving the results of CT.

Dataset Information

Loss of miR-673-5p expression in the cornea promotes rat corneal allograft rejection by promoting Th17 cell differentiation mediated by JAK2/STAT3.

Background

Methods

Results

Conclusions

Publications

Loss of miR-673-5p expression in the cornea promotes rat corneal allograft rejection by promoting Th17 cell differentiation mediated by JAK2/STAT3.

Similar Datasets

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