2. Academic Validation
  3. Anti-Na+/K+-ATPase DR antibody attenuates UUO-induced renal fibrosis through inhibition of Na+/K+-ATPase α1-dependent HMGB1 release

Anti-Na+/K+-ATPase DR antibody attenuates UUO-induced renal fibrosis through inhibition of Na+/K+-ATPase α1-dependent HMGB1 release

  • Int Immunopharmacol. 2023 Feb 9;116:109826. doi: 10.1016/j.intimp.2023.109826.
Jin Zheng 1,  Ping Lan 1,  Meihe Li 1,  Min-Chao Kang 2,  Meng Xun 3,  Xiangyun Ma 2,  Mengyao Yan 2,  Dan Sun 2,  Yu Shen 2,  Xinyi Fu 2,  Xiaoming Ding 4,  Xiaofei Yan 5,  Wu-Jun Xue 6
Affiliations

Affiliations

  • 1 Hospital of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China.
  • 2 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China.
  • 3 Department of Microbiology and Immunology, Xi'an Jiaotong University, Xi'an 710061, China.
  • 4 Hospital of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China; Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China; Department of Microbiology and Immunology, Xi'an Jiaotong University, Xi'an 710061, China.
  • 5 Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Xi'an Jiaotong University, Xi'an, 710061, China. Electronic address: yanxiaofei@xjtu.edu.cn.
  • 6 Hospital of Nephrology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, China. Electronic address: xwujun126@xjtu.edu.cn.
PMID: 36764269 DOI: 10.1016/j.intimp.2023.109826
Abstract

Reduced Na+/K+-ATPase (NKA) activity and NKAα1 expression are engaged in the pathologies of renal diseases. NKA-mediated Src activation is not the only reason for NKA-related renal fibrosis. In this study, we found that genetic reduction of NKAα1 exhibited exacerbated tubulointerstitial lesions and fibrosis in the UUO mice model. Activation of NKAα1 with an antibody against the extracellular DR region of the NKAα1 subunit (DRm217) prevented UUO-induced tubulointerstitial lesions, preserved kidney function, and decrease renal fibrosis. Further studies revealed that NKAα1 deficiency mice exhibited high inflammation factors expression when they suffered UUO surgery, compared with NKAα1+/+ (WT) mice. DRm217 alleviated inflammatory cell infiltration, suppress NF-κB phosphorylation, and decreased inflammatory factors expression in the UUO mice model. Released HMGB1 can trigger the inflammatory response and contribute to renal fibrosis. Knockdown of NKA in renal tubular cells or in NKAα1+/- mice was associated with more susceptibility to HMGB1 release in the UUO mice model. DRm217 exerted its antifibrotic effect via inhibiting HMGB1 release. Furthermore, AMPK activation participates in the effect of DRm217 on inhibiting HMGB1 release. Our findings suggest that NKAα1 is a regulator of renal fibrosis and its DR-region is a novel target on it.

Keywords

DRm217; HMGB1; Inflammation; Na(+)/K(+)-ATPase; Renal fibrosis.

Figures
Products
Inhibitors & Agonists
Other Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z