Isoliquiritigenin Attenuates UUO-Induced Renal Inflammation and Fibrosis by Inhibiting Mincle/Syk/NF-Kappa B Signaling Pathway
| Autor: | Liao,Yuan, Tan,Rui-zhi, Li,Jian-chun, Liu,Tong-tong, Zhong,Xia, Yan,Ying, Yang,Jie-ke, Lin,Xiao, Fan,Jun-ming, Wang,Li |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Lipopolysaccharides
Male Mincle Administration Oral macrophage Isoliquiritigenin urologic and male genital diseases Kidney Protective Agents Mice Structure-Activity Relationship Chalcones Transforming Growth Factor beta CKD Animals Syk Kinase Lectins C-Type Cells Cultured Original Research Inflammation Drug Design Development and Therapy Dose-Response Relationship Drug Molecular Structure Macrophages fibrosis NF-kappa B Membrane Proteins Mice Inbred C57BL Signal Transduction Ureteral Obstruction |
| Zdroj: | Drug Design, Development and Therapy |
| ISSN: | 1177-8881 |
| Popis: | Yuan Liao,1,* Rui-zhi Tan,1,* Jian-chun Li,1 Tong-tong Liu,1 Xia Zhong,1 Ying Yan,1 Jie-ke Yang,1 Xiao Lin,1 Jun-ming Fan,2 Li Wang1 1Research Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 2Chengdu Medical College, Chengdu, Sichuan 610000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li WangResearch Center of Combine Traditional Chinese and Western Medicine, Affiliated Traditional Medicine Hospital, Southwest Medical University, 319 # Zhongshan Road, Luzhou, Sichuan 646000, People’s Republic of ChinaTel +86 0830 3161222Email wangli120@swmu.edu.cnPurpose: Chronic kidney disease (CKD) is a global nephrotic syndrome characterized by chronic inflammation, oxidative stress and fibrosis in the kidney. Isoliquiritigenin (ISL), a flavonoid from licorice, has historically been reported to inhibit innate immune responses to inflammation and fibrosis in vivo. However, the effect of ISL on CKD progression is largely unknown.MaterialsandMethods: In this study, we employed the inflammatory and fibrotic models of LPS/TGF-β-induced bone marrow-derived macrophages (BMDM) in vitro and unilateral ureteral obstruction (UUO) model in vivo to explore the potential effects and mechanism of ISL on renal inflammation and fibrosis.Results: Our results manifest that ISL improved UUO-induced renal dysfunction and reduced tubular damage with a significantly downregulated mRNA expression and secretion of IL-1β, IL-6, TNF-α and MCP-1 in vitro and in vivo. Itis worth noting that ISL can strongly inhibit the mRNA and protein expression of Mincle (macrophage-induced c-type lectin) in BMDM and UUO. ISL inhibited the phosphorylation of Syk and NF-kappa B and simultaneously reduced the expression of α-SMA and Col III in vivo and in vitro. More interestingly, when dealing with TDB, a ligand of Mincle, it revealed significant reversal of protein expression levels as that observed with ISL. The expressions of IL-1β, IL-6, TNF-α, iNOS, p-Syk, p-NF-kappa B, α-SMA and FN in BMDM inflammatory model were significantly upregulated with TDB treatment. This confirms that ISL inhibits inflammation and fibrosis of macrophage by suppressing Mincle/Syk/NF-kappa B signaling pathway.Conclusion: To conclude, ISL protects UUO-induced CKD by inhibiting Mincle-induced inflammation and suppressing renal fibrosis, which might be a specific renal protective mechanism of ISL, making it a novel drug to ameliorate CKD.Keywords: Isoliquiritigenin, Mincle, macrophage, CKD, inflammation, fibrosis |
| Databáze: | OpenAIRE |
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