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- Title
Neuraminidase 1 promotes renal fibrosis development in male mice.
- Authors
Chen, Qian-Qian; Liu, Kang; Shi, Ning; Ma, Gaoxiang; Wang, Peipei; Xie, Hua-Mei; Jin, Si-Jia; Wei, Ting-Ting; Yu, Xiang-Yu; Wang, Yi; Zhang, Jun-Yuan; Li, Ping; Qi, Lian-Wen; Zhang, Lei
- Abstract
The functions of the influenza virus neuraminidase has been well documented but those of the mammalian neuraminidases remain less explored. Here, we characterize the role of neuraminidase 1 (NEU1) in unilateral ureteral obstruction (UUO) and folic acid (FA)-induced renal fibrosis mouse models. We find that NEU1 is significantly upregulated in the fibrotic kidneys of patients and mice. Functionally, tubular epithelial cell-specific NEU1 knockout inhibits epithelial-to-mesenchymal transition, inflammatory cytokines production, and collagen deposition in mice. Conversely, NEU1 overexpression exacerbates progressive renal fibrosis. Mechanistically, NEU1 interacts with TGFβ type I receptor ALK5 at the 160-200aa region and stabilizes ALK5 leading to SMAD2/3 activation. Salvianolic acid B, a component of Salvia miltiorrhiza, is found to strongly bind to NEU1 and effectively protect mice from renal fibrosis in a NEU1-dependent manner. Collectively, this study characterizes a promotor role for NEU1 in renal fibrosis and suggests a potential avenue of targeting NEU1 to treat kidney diseases. The influenza virus neuraminidase has been well documented, yet the functions of mammalian neuraminidases remain less explored. Here, the authors show that neuraminidase 1 promotes renal fibrosis development by interacting with ALK5 to activate SMAD2/3.
- Subjects
RENAL fibrosis; EPITHELIAL-mesenchymal transition; URETERIC obstruction; SALVIA miltiorrhiza; FOLIC acid; NEURAMINIDASE
- Publication
Nature Communications, 2023, Vol 14, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-023-37450-8