tetano
Editor, Senior Moderator
Nat Commun
. 2023 Mar 27;14(1):1713.
doi: 10.1038/s41467-023-37450-8.
Neuraminidase 1 promotes renal fibrosis development in male mice
Qian-Qian Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Kang Liu[SUP] #[/SUP][SUP] 3 [/SUP], Ning Shi[SUP] #[/SUP][SUP] 4 [/SUP], Gaoxiang Ma[SUP] 5 [/SUP], Peipei Wang[SUP] 6 [/SUP], Hua-Mei Xie[SUP] 5 [/SUP], Si-Jia Jin[SUP] 4 [/SUP], Ting-Ting Wei[SUP] 1 [/SUP], Xiang-Yu Yu[SUP] 1 [/SUP], Yi Wang[SUP] 5 [/SUP], Jun-Yuan Zhang[SUP] 1 [/SUP], Ping Li[SUP] 1 [/SUP], Lian-Wen Qi[SUP] 7 8 9 [/SUP], Lei Zhang[SUP] 10 11 [/SUP]
Affiliations
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.
. 2023 Mar 27;14(1):1713.
doi: 10.1038/s41467-023-37450-8.
Neuraminidase 1 promotes renal fibrosis development in male mice
Qian-Qian Chen[SUP] #[/SUP][SUP] 1 2 [/SUP], Kang Liu[SUP] #[/SUP][SUP] 3 [/SUP], Ning Shi[SUP] #[/SUP][SUP] 4 [/SUP], Gaoxiang Ma[SUP] 5 [/SUP], Peipei Wang[SUP] 6 [/SUP], Hua-Mei Xie[SUP] 5 [/SUP], Si-Jia Jin[SUP] 4 [/SUP], Ting-Ting Wei[SUP] 1 [/SUP], Xiang-Yu Yu[SUP] 1 [/SUP], Yi Wang[SUP] 5 [/SUP], Jun-Yuan Zhang[SUP] 1 [/SUP], Ping Li[SUP] 1 [/SUP], Lian-Wen Qi[SUP] 7 8 9 [/SUP], Lei Zhang[SUP] 10 11 [/SUP]
Affiliations
- PMID: 36973294
- DOI: 10.1038/s41467-023-37450-8
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.