Targeting Neuraminidase 4 Attenuates Kidney Fibrosis in Mice.

Autor: Xiao PT; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China., Hao JH; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China., Kuang YJ; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China., Dai CX; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China., Rong XL; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China., Jiang LL; PolyU Academy for Interdisciplinary Research, The Hong Kong Polytechnic University, Hong Kong, 999077, China., Xie ZS; Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, 450000, China., Zhang L; Hunan Key Laboratory of Kidney Disease and Blood Purification, Department of Nephrology, The Second Xiangya Hospital Central South University, Changsha, 410000, China., Chen QQ; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China., Liu EH; School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China.; State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 Oct; Vol. 11 (39), pp. e2406936. Date of Electronic Publication: 2024 Aug 13.
DOI: 10.1002/advs.202406936
Abstrakt: Despite significant progress in therapy, there remains a lack of substantial evidence regarding the molecular factors that lead to renal fibrosis. Neuraminidase 4 (NEU4), an enzyme that removes sialic acids from glycoconjugates, has an unclear role in chronic progressive fibrosis. Here, this study finds that NEU4 expression is markedly upregulated in mouse fibrotic kidneys induced by folic acid or unilateral ureter obstruction, and this elevation is observed in patients with renal fibrosis. NEU4 knockdown specifically in the kidney attenuates the epithelial-to-mesenchymal transition, reduces the production of pro-fibrotic cytokines, and decreases cellular senescence in male mice. Conversely, NEU4 overexpression exacerbates the progression of renal fibrosis. Mechanistically, NEU4 254-388aa interacts with Yes-associated protein (YAP) at WW2 domain (231-263aa), promoting its nucleus translocation and activation of target genes, thereby contributing to renal fibrosis. 3,5,6,7,8,3',4'-Heptamethoxyflavone, a natural compound, is identified as a novel NEU4 inhibitor, effectively protecting mice from renal fibrosis in a NEU4-dependent manner. Collectively, the findings suggest that NEU4 may represent a promising therapeutic target for kidney fibrosis.
(© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
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