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

Ying Gao, Wenqiang Yu, Jinfang Song, Jiayi Nie, Zichan Cui, Shihong Wen, Benquan Liu, Hua Liang

Hypertension research : official journal of the Japanese Society of Hypertension 2023 Aug

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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. © 2023. The Author(s), under exclusive licence to The Japanese Society of Hypertension.

Citation

Ying Gao, Wenqiang Yu, Jinfang Song, Jiayi Nie, Zichan Cui, Shihong Wen, Benquan Liu, Hua Liang. JMJD3 ablation in myeloid cells confers renoprotection in mice with DOCA/salt-induced hypertension. Hypertension research : official journal of the Japanese Society of Hypertension. 2023 Aug;46(8):1934-1948