Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells

Jia, Qianqian; Wang, Jiancheng; Long, Jing; Zhao, Yan; Chen, Si-Jia; Zhai, Jiadai; Wei, Lianbo; Zhang, Quan; Chen, Yue; Long, Haibo

doi:10.3390/molecules181013061

Cited by 45 publications

(28 citation statements)

References 44 publications

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“…In diabetic nephropathy, high glucose can activate NF-κB and promote the infiltration of inflammatory cells into renal interstitium, leading to ECM accumulation and renal interstitial fibrosis. 26,27 Moreover, the NF-κB superfamily of transcription factors plays an important role in the regulation of renal fibrosis. 28 We found the JSH-23 treatment of HE4-transfected HK2 cells effectively abolished HE4-inhibited MMP2 expression.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia‐induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF‐κB

et al. 2019

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Hypoxia-induced extracellular matrix (ECM) deposition is an important cause of renal fibrosis that is triggered by unknown mechanisms. Human epididymis secretory protein 4 (HE4) is a newly discovered key molecule that causes ECM deposition. We used the unilateral ureteral obstruction (UUO) mouse model to investigate the expression and mechanisms of HE4 in the pathogenesis of renal fibrosis. Results were confirmed in the HK2 cell line and in human donors of kidney tissue with chronic kidney disease. Hypoxia significantly increased HE4 in renal tubular epithelial cells. HE4 overexpression activated the NF-κB pathway through the NF-κB transcription-activating group P65 by phosphorylation and nuclear translocation.NF-κB upregulated tissue inhibitor metalloproteinases 1, which may inhibit ECM degradation through inhibition of matrix metallopeptidase 2 activity. Silencing HE4 inhibited hypoxia-induced ECM deposition and alleviated fibrosis in UUO mice in vivo and blocked NF-κB activation in vitro. Expression of HE4 in the tubulointerstitium was positively correlated with tubulointerstitial fibrosis in tissue samples from patients with chronic kidney disease. Our results suggest that hypoxia induces renal fibrosis by upregulating HE4 and activating the HIF-1α/HE4/NF-κB signaling pathway. Uncovering the molecular mechanisms and function of HE4 overexpression in hypoxia-induced renal fibrosis will provide important insights into understanding renal fibrosis and antifibrotic strategies. K E Y W O R D Schronic hypoxia, extracellular matrix, human epididymis secretory protein 4, NF-κB, renal fibrosis

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Section: Discussionmentioning

confidence: 99%

Hypoxia‐induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF‐κB

et al. 2019

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“…Recently, we demonstrated that SLs, including PTL, micheliolide (MCL), and several synthetic analogs of these molecules, could effectively attenuate the high glucose-stimulated and AOPP-induced activation of NF- κ B, the degradation of I κ B α , and the expression of MCP-1 in rat mesangial cells (MCs) [ 30 , 31 ]. These findings showed that SLs can exert a beneficial role in high glucose-stimulated and AOPPs-induced inflammation and ECM deposition by preventing NF- κ B activation in MCs.…”

Section: Introductionmentioning

confidence: 99%

Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF-κB-Dependent Mechanism

Zhao

Chen

Wang

et al. 2015

Oxidative Medicine and Cellular Longevity

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Inflammation is a relevant factor in the pathogenesis of diabetes nephropathy (DN). Sesquiterpene lactones (SLs), originally isolated from Tanacetum parthenium, have been reported to exhibit anti-inflammatory effects but few studies have examined their effects on DN. To determine whether advanced oxidation protein products (AOPPs) can induce the expression of chemokine monocyte chemoattractant protein- (MCP-) 1 in cultured mouse podocytes and to explore the mechanisms of the potential renoprotection of SLs, we treated podocytes with AOPPs and SLs (parthenolide and its derivatives micheliolide, compound 1, and compound 2). MCP-1 mRNA and protein expression were tested using quantitative real-time PCR and ELISA, respectively, and the protein levels of IKKβ, phospho-IKKβ, IκBα, NF-κB p65, phospho-NF-κB p65, and tubulin were analyzed by Western blotting. AOPPs activated the expression of MCP-1 mRNA and protein in a dose- and time-dependent manner, activated IKKβ and NF-κB p65, and promoted IκBα degradation. The IKK/NF-κB inhibitor parthenolide decreased AOPP-induced MCP-1 expression. Pretreatment with SLs inhibited MCP-1 mRNA and protein expression and suppressed IKKβ and NF-κB p65 phosphorylation and IκBα degradation. Taken together, these findings provide a novel explanation for the anti-inflammatory effects of SLs that will ultimately benefit DN and potentially other inflammatory and immune renal diseases.

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“…It is speculated that HMGB1-NF-κB may function as a signaling pathway in renal diseases. Previous studies revealed that TGF-β1 was regulated by NF-κB in certain signaling pathways, which indicates a potential role for NF-κB (45,46). Therefore, the present study aimed to investigate the association between HMGB1, NF-κB, TGF-β1 and CAN.…”

Section: Discussionmentioning

confidence: 93%

HMGB1, TGF‑β and NF‑κB are associated with chronic allograft nephropathy

2017

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Sesquiterpene Lactones and Their Derivatives Inhibit High Glucose-Induced NF-κB Activation and MCP-1 and TGF-β1 Expression in Rat Mesangial Cells

Cited by 45 publications

References 44 publications

Hypoxia‐induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF‐κB

Hypoxia‐induced HE4 in tubular epithelial cells promotes extracellular matrix accumulation and renal fibrosis via NF‐κB

Sesquiterpene Lactones Inhibit Advanced Oxidation Protein Product-Induced MCP-1 Expression in Podocytes via an IKK/NF-κB-Dependent Mechanism

HMGB1, TGF‑β and NF‑κB are associated with chronic allograft nephropathy

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