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Abnormal epigenetic memory of mesenchymal stem and progenitor cells caused by fetal malnutrition induces hypertension and renal injury in adulthood

Hypertension Research volume 47, pages 2405–2415 (2024)Cite this article

A Comment to this article was published on 13 August 2024

Abstract

Fetal malnutrition has been reported to induce hypertension and renal injury in adulthood. We hypothesized that this hypertension and renal injury would be associated with abnormal epigenetic memory of stem and progenitor cells contributing to organization in offspring due to fetal malnutrition. We measured blood pressure (BP) for 60 weeks in offspring of pregnant rats fed a normal protein diet (Control), low-protein diet (LP), and LP plus taurine (LPT) in the fetal period. We used western blot analysis to evaluate the expression of αSMA and renin in CD44-positive renal mesenchymal stem cells (MSCs) during differentiation by TGF-β1. We measured kidney label-retaining cells (LRCs) at 11 weeks of age and formation of endothelial progenitor cells (EPCs) at 60 weeks of age from the offspring with fetal malnutrition. Epigenetics of the renal MSCs at 14 weeks were investigated by ATAC-sequence and RNA-sequence analyses. BP was significantly higher in LP than that in Control and LPT after 45–60 weeks of age. Numbers of LRCs and EPC colonies were significantly lower in LP than in Control. Renal MSCs from LP already showed expression of h-caldesmon, αSMA, LXRα, and renin before their differentiation. Epigenetic analyses identified PAR2, Chac1, and Tspan6 genes in the abnormal differentiation of renal MSCs. These findings suggested that epigenetic abnormalities of stem and progenitor cell memory cause hypertension and renal injury that appear in adulthood of offspring with fetal malnutrition.

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Acknowledgements

The authors would like to thank Akiko Tsunemi and Mayumi Katakawa for their technical support.

Funding

This study was supported by financial grants from the JSPS KAKENHI Grant Numbers JP18K07831 and JP22K15908.

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Authors and Affiliations

  1. Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan

    Shoichi Shimizu & Ichiro Morioka

  2. Division of Cell Regeneration and Transplantation, Department of Functional Morphology, Nihon University School of Medicine, Tokyo, Japan

    Noboru Fukuda, Lan Chen & Taro Matsumoto

  3. Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Atsushi Kaneda

  4. Faculty of Human Health Science, Hachinohe Gakuin University, Hachinohe, Aomori, Japan

    Morito Endo

  5. Department of Pharmacology, Kagawa University School of Medicine, Takamatsu, Kagawa, Japan

    Akira Nishiyama

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  1. Shoichi Shimizu
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Correspondence to Noboru Fukuda.

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Shimizu, S., Fukuda, N., Chen, L. et al. Abnormal epigenetic memory of mesenchymal stem and progenitor cells caused by fetal malnutrition induces hypertension and renal injury in adulthood. Hypertens Res 47, 2405–2415 (2024). https://doi.org/10.1038/s41440-024-01756-x

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