S100A9 promotes renal calcium oxalate stone formation via activating the TLR4-p38/MAPK-LCN2 signaling pathway.

Autor: Wang Q; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China. Electronic address: wangqing1@gz5055.com., Chen X; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China., Huang K; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China., Deng G; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China., Tian Y; Department of Urology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550000, China. Electronic address: tygz2024@163.com., Jiang K; Department of Urology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, China. Electronic address: jiangkehua@gz5055.com.
Jazyk: angličtina
Zdroj: International journal of biological macromolecules [Int J Biol Macromol] 2024 Nov; Vol. 281 (Pt 1), pp. 136178. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1016/j.ijbiomac.2024.136178
Abstrakt: Objectives: To explore the role of S100A9 protein in renal calcium oxalate (CaOx) stone formation.
Methods: CaOx nephrocalcinosis mice were established via intraperitoneal injection of glyoxylate. They were treated with S100A9 deficiency, Paquinimod, or p38 MAPK-IN-1. Vonkossa staining was conducted to observe the deposition of CaOx crystals. Renal expression of inflammation, macrophage polarization, and injury markers was detected using immunohistochemistry and qPCR. Effects of S100A9 on renal tubular epithelial cells (HK-2) were explored by transcriptome sequencing. The mechanism of how S100A9 regulated lipocalin 2 (LCN2) was studied through Western Blot. Flow cytometry was performed to detect the influence of LCN2 on macrophages polarization.
Results: S100A9 deficiency inhibited the renal deposition of CaOx crystals in nephrocalcinosis mice. S100A9 upregulated the expression of LCN2 in HK-2 cells via activating the TLR4-p38/MAPK pathway. LCN2 promoted the migration and M1 polarization of macrophages. S100A9 deficiency downregulated the renal expression of LCN2, IL1-β, Kim-1, F4/80, and CD80 in nephrocalcinosis mice. Paquinimod and p38 MAPK-IN-1 both inhibited the renal deposition of CaOx crystals and downregulated the expression of LCN2, IL1-β, Kim-1, F4/80, iNOS, and CD68 in nephrocalcinosis mice.
Conclusions: S100A9 promotes renal inflammatory injury by activating the TLR4-p38/MAPK-LCN2 pathway and then contributes to CaOx stone formation.
Competing Interests: Declaration of competing interest Wang Qing reports financial support was provided by National Natural Science Foundation of China. Wang Qing reports financial support was provided by The Guizhou Provincial Science and Technology Project. Wang Qing reports financial support was provided by Subsidy funding for the 2021 National Natural Science Foundation of China. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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