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Human placenta mesenchymal stem cell-derived exosome shuttling microRNA-130b-3p from gestational diabetes mellitus patients targets ICAM-1 and perturbs human umbilical vein endothelial cell angiogenesis

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Abstract

Objective

The aim of this study was to investigate the roles of miR-130b-3p and ICAM-1 in gestational diabetes mellitus (GDM) and their potential association.

Methods

Human placenta mesenchymal stem cells (PlaMSCs) were isolated from GDM patients, and the effects of the PlaMSCs from GDM patients (GDM-MSCs) and the exosomes secreted by GDM-MSCs on human umbilical vein endothelial cell (HUVEC) proliferation, migration, and angiogenesis were detected. Next, GDM-MSCs were transfected with miR-130b-3p antagomir to modify miR-130b-3p expression in GDM-MSCs-derived exosomes, and the exosomes with modified miR-130b-3p expression were cultured with HUVECs to evaluate exosomal miR-130b-3p on HUVEC function. Furthermore, a target gene of miR-130b-3p was predicted and assessed. The miR-130b-3p-modified exosomes were cultured with HUVECs transfected with ICAM-1 shRNA to determine the effect of miR-130b-3p-ICAM-1 crosstalk on HUVEC function. Additionally, a GDM mouse model was conducted to further study the effect of miR-130b-3p in GDM in vivo.

Results

GDM-MSCs inhibited HUVEC proliferation and angiogenesis. The elevated expression of miR-130b-3p was found in GDM-MSCs-derived exosomes. GDM-MSCs-derived exosomes repressed the proliferation and angiogenesis of HUVECs and miR-130b-3p inhibition could restrain the inhibition of the exosomes on HUVEC function. Mechanistically, miR-130b-3p downregulated ICAM-1 expression in a targeted manner, and thereby enhanced HUVEC proliferation, migration, and angiogenesis and increased the expression of angiogenesis-related factors. Moreover, miR-130b-3p inhibition promoted placental angiogenesis in GDM mice and upregulated ICAM-1 expression.

Conclusion

Conclusively, GDM-MSCs-derived exosomes shuttling miR-130b-3p repressed proliferation, migration, and angiogenesis of HUVECs by regulating ICAM-1 expression.

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Availability of data and materials

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

Not applicable.

Funding

Thanks for the grant from the General Project of Natural Science Foundation of Hunan Province (Grant No. 2021JJ31024).

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Author notes

  1. Zhou Gao and Nan Wang have contributed equally to this research.

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, The Third Xiangya Hospital of Central South University, Changsha, 410013, Hunan, People’s Republic of China

    Zhou Gao, Nan Wang & Xinli Liu

Authors
  1. Zhou Gao
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  2. Nan Wang
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  3. Xinli Liu
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Contributions

GZ and WN contributed equally to the manuscript, GZ, WN, and LXL had full access to all of the data in the study and takes responsibility for the integrity of the data, the accuracy of the data analysis, GZ, WN, and LXL wrote the manuscript draft. GZ, WN, and LXL performed research. GZ and WN contributed substantially to the study design and the writing of the manuscript. GZ, WN, and LXL contributed to the manuscript preparation and statistical analysis. All authors read and approved the final version of the manuscript.

Corresponding author

Correspondence to Xinli Liu.

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Conflict of interest

The author declares no competing financial interests.

Ethics approval

This work was authorized by The Third Xiangya Hospital of Central South University, and written informed consent was collected from all participants.

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Informed consent to participate in the study was obtained from participants.

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This article belongs to the topical collection Pregnancy and Diabetes, managed by Antonio Secchi and Marina Scavini.

Supplementary Information

Below is the link to the electronic supplementary material.

592_2022_1910_MOESM1_ESM.tif

Supplementary file1 The expression of exosome markers CD9, CD63, and a endoplasmic reticulum maker Calnexin in the isolated exosomes was detected by western blot. Notes: A, CD9 expression was measured by western blot. B, CD63 expression was tested by western blot. C, Calnexin expression was evaluated by western blot. In addition to Marker, the bands from left to right in the figures sequentially represents the CON-MSCs, GDM -MSCs, CON-PdEs, GDM-PdEs, and CON-PdEs and GDM-PdEs isolated after GW4869 addition. CON-PdEs, exosomes derived by CON-MSCs; GDM-PdEs, exosomes derived by GDM-MSCs; CON-MSCs, PlaMSC from healthy volunteers; GDM-MSCs, PlaMSCs from GDM patients; GDM, gestational diabetes mellitus; PlaMSCs, mesenchymal stem cells from placenta (TIF 54838 kb)

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Gao, Z., Wang, N. & Liu, X. Human placenta mesenchymal stem cell-derived exosome shuttling microRNA-130b-3p from gestational diabetes mellitus patients targets ICAM-1 and perturbs human umbilical vein endothelial cell angiogenesis. Acta Diabetol 59, 1091–1107 (2022). https://doi.org/10.1007/s00592-022-01910-2

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  • DOI: https://doi.org/10.1007/s00592-022-01910-2

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