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JMJD3 ablation in myeloid cells confers renoprotection in mice with DOCA/salt-induced hypertension

Hypertension Research volume 46, pages 1934–1948 (2023)Cite this article

Abstract

Hypertension-induced renal injury is characterized by robust inflammation and tubulointerstitial fibrosis. Jumonji domain containing-3 (JMJD3) is closely linked with inflammatory response and fibrogenesis. Here we examined the effect of myeloid JMJD3 ablation on kidney inflammation and fibrosis in deoxycorticosterone acetate (DOCA)/salt hypertension. Our results showed that JMJD3 is notably induced in the kidneys with hypertensive injury. DOCA/salt stress causes an elevation in blood pressure that was no difference between myeloid specific JMJD3-deficient mice and wild-type control mice. Compared with wild-type control mice, myeloid JMJD3 ablation ameliorated kidney function and injury of mice in response to DOCA/salt challenge. Myeloid JMJD3 ablation attenuated collagen deposition, extracellular matrix proteins expression, and fibroblasts activation in injured kidneys following DOCA/salt treatment. Furthermore, myeloid JMJD3 ablation blunts inflammatory response in injured kidneys after DOCA/salt stress. Finally, myeloid JMJD3 ablation precluded myeloid myofibroblasts activation and protected against macrophages to myofibroblasts transition in injured kidneys. These beneficial effects were accompanied by reduced expression of interferon regulator factor 4. In summary, JMJD3 ablation in myeloid cells reduces kidney inflammation and fibrosis in DOCA salt-induced hypertension. Inhibition of myeloid JMJD3 may be a novel potential therapeutic target for hypertensive nephropathy.

Myeloid JMJD3 deficiency reduces inflammatory response, myeloid fibroblasts activation, macrophages to myofibroblasts transition, and delays kidney fibrosis progression.

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Acknowledgements

We thank Dr. Chaoqun Zhong for her assistance with the schematic diagram.

Funding

This study was supported by grants from National Natural Science Foundation of China (No. 81871539), Natural Science Foundation of Guangdong Province (No. 2021A1515011481) and Special Fund of Foshan Summit Plan (2019C001, 2019D004).

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Author notes

  1. These authors contributed equally: Ying Gao, Wenqiang Yu

Authors and Affiliations

  1. Department of Anesthesiology, The First People’s Hospital of Foshan, Foshan, 528000, China

    Ying Gao, Jiayi Nie & Benquan Liu

  2. Department of Anesthesiology, Foshan Women and Children Hospital, Foshan, 528000, China

    Wenqiang Yu, Zichan Cui & Hua Liang

  3. Zhuhai Campus, Zunyi Medical University, Zhuhai, 519041, China

    Jinfang Song

  4. Department of Anesthesiology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, 510080, China

    Shihong Wen

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Contributions

YG and HL conceived and designed the research. YG, BL, and WY performed the experiments. YG, BL, JS, and JN analyzed the data. BL, JS, SW, and ZC interpreted the results of experiments. WY and HL drafted the manuscript. HL edited and revised the manuscript. All authors contributed to the article and approved the submitted version.

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Correspondence to Benquan Liu or Hua Liang.

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Gao, Y., Yu, W., Song, J. et al. JMJD3 ablation in myeloid cells confers renoprotection in mice with DOCA/salt-induced hypertension. Hypertens Res 46, 1934–1948 (2023). https://doi.org/10.1038/s41440-023-01312-z

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