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microRNA-140-5p from human umbilical cord mesenchymal stem cells–released exosomes suppresses preeclampsia development

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Abstract

This work unraveled the action of human umbilical cord mesenchymal stem cells–released exosomes (huc-MSCs-EXO) transfer of miR-140-5p in preeclampsia (PE). miR-140-5p and follistatin-like 3 (FSTL3) expression in placental tissues of PE patients was tested. EXO were isolated from huc-MSCs. Hypoxic trophoblast cells were co-cultured with huc-MSCs-EXO. Cell biological functions, angiogenesis, and inflammation were evaluated. Suppressed miR-140-5p and induced FSTL3 levels were measured in PE. Huc-MSCs-EXO drove biological functions and angiogenesis while hindering inflammation in hypoxic trophoblast cells. Increasing miR-140-5p further improved the positive role of huc-MSCs-EXO for hypoxic trophoblast cells, but the miR-140-5p-mediated effect in hypoxic trophoblast cells was abrogated by overexpressing FSTL3. miR-140-5p from huc-MSCs-EXO suppresses PE through repressing FSTL3.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Funding

This work was supported by National Key Research and Development Program of China (No. 2018YFC1002804), and National Natural Science Foundation of China (No. 81771662, 81771618, 81971356).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, No.238 Jiefang Road, Wuchang, Wuhan, 430000, Hubei, China

    Yan Jiang, Ting Luo, Jinhua Tian & Jing Yang

  2. Department of Urology, General Hospital of Central Command Theater in PLA, Wuhan, 430000, Hubei, China

    Qiang Xia

Authors
  1. Yan Jiang
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  2. Ting Luo
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  3. Qiang Xia
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  4. Jinhua Tian
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  5. Jing Yang
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Correspondence to Jing Yang.

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Yan Jiang and Ting Luo are co-first authors.

Supplementary Information

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Supplementary Figure 1

Identification of huc-MSCs-derived EXO. A. The size of EXO was assessed by NTA; B. Morphology of EXO was observed by TEM; C. Markers of EXO was analyzed by Western blot. (JPG 1.06 MB)

Supplementary Figure 2

Huc-MSCs-EXO encourages the development of hypoxic trophoblast cells. A. Apoptosis of HTR-8/SVneo cells was measured by flow cytometry in response to huc-MSCs-EXO treatment; B. Tube forming ability HTR-8/SVneo cells was tested by tube formation assay in response to huc-MSCs-EXO treatment. The data were all measurement data and expressed as mean ± standard deviation; # P < 0.05 vs. NP group; % P < 0.05 vs. the PE group. (JPG 1.70 MB)

Supplementary Figure 3

Huc-MSCs-EXO carrying miR-140-5p has a better effect to protect hypoxic trophoblast cells. A. Apoptosis of HTR-8/SVneo cells was measured by flow cytometry upon treatment of huc-MSCs-EXO carrying miR-140-5p; B. Tube forming ability HTR-8/SVneo cells was tested by tube formation assay upon treatment of huc-MSCs-EXO carrying miR-140-5p. The data were all measurement data and expressed as mean ± standard deviation; % P < 0.05 vs. the EXO-miR-140-5p NC group. (JPG 2.00 MB)

Supplementary Figure 4

Suppression of FSTL3 drives the growth of hypoxic trophoblast cells. A. Apoptosis of HTR-8/SVneo cells was analyzed by flow cytometry with suppression of FSTL3; B. Tube forming ability HTR-8/SVneo cells was tested by tube formation assay with suppression of FSTL3. The data were all measurement data and expressed as mean ± standard deviation; # P < 0.05 vs. the sh-NC group. (JPG 1.91 MB)

Supplementary Figure 5

miR-140-5p from huc-MSCs-EXO accelerates the development of hypoxic trophoblast cells through targeting FSTL3. A. Apoptosis of HTR-8/SVneo cells was measured by flow cytometry after being treated with EXO- miR-140-5p mimic + oe-FSTL3; B. Tube forming ability HTR-8/SVneo cells was tested by tube formation assay after being treated with EXO-miR-140-5p mimic + oe-FSTL3. The data were all measurement data and expressed as mean ± standard deviation; # P < 0.05 vs. the EXO-miR-140-5p mimic + oe-NC group. (JPG 2.03 MB)

Supplementary file6 (DOCX 12.8 KB)

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Jiang, Y., Luo, T., Xia, Q. et al. microRNA-140-5p from human umbilical cord mesenchymal stem cells–released exosomes suppresses preeclampsia development. Funct Integr Genomics 22, 813–824 (2022). https://doi.org/10.1007/s10142-022-00848-6

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