Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway

Huang, Junying; Chen, Zhiquan; Li, Jie; Chen, Qiuhong; Li, Jingyan; Gong, Wenyan; Huang, Jiani; Liu, Peiqing; Huang, Heqing

doi:10.1016/j.bcp.2017.02.016

Cited by 30 publications

(23 citation statements)

References 44 publications

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“…However, when cells were stimulated by cytokines, virus and oxidative stress, NF-κB was activated and then transferred to the nucleus to regulate gene transcription. Previous studies have showed that the NF-κB is closely related to a variety of signal transduction in cells, and also plays an important role in the process of development of renal interstitial fibrosis [32]. The NF-κB is extensively expressed in renal glomerular cells and renal tubular epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via the TLR4/NF-kB Signaling Pathway

Liu

Xiong

et al. 2017

Am J Nephrol

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Background: Hyperuricemia is an independent risk factor for causing chronic kidney disease and contributes to kidney fibrosis. After urate crystals get deposited in the kidney, they can cause hyperuricemia nephropathy, leading to glomerular hypertrophy and renal tubular interstitial fibrosis. Recent data showed that uric acid (UA) could induce epithelial mesenchymal transition (EMT) of renal tubular cells, in which NRLP3 inflammatory pathway was involved. However, whether TLR4/NF-κB signaling pathway is also involved in EMT of renal tubular cells induced by UA is not clear. Methods: Human renal tubular epithelial cells (HK-2) were directly treated with UA and the phenotypic transition was detected by morphological changes and the molecular markers of EMT. The activation of the TLR4/NF-κB signaling pathway induced by UA was measured by Western blot and its involvement was further confirmed by the inhibition of NF-κB activation or knockdown of toll like receptor 4 (TLR4) expression. Results: UA induced obvious morphological changes of HK-2 cell, accompanied with altered molecular markers of EMT including fibronectin, α-SMA and E-cadherin. In addition, UA significantly upregulated the gene expression of interleukin-1β and tumor necrosis factor-α in a time- and dose-dependent manner. Furthermore, UA significantly activated the TLR4/NF-κB signaling pathway in HK-2 cells, while the inhibition of the TLR4 expression by siRNA and NF-κB activation by PDTC significantly attenuated EMT induced by UA in HK-2 cells. Conclusions: UA can induce EMT in renal tubular epithelial cells by the activation of the TLR4/NF-κB signaling pathway, and the targeted intervention of the TLR4/NF-κB signaling pathway might effectively inhibit UA-induced renal interstitial fibrosis mediated by EMT.

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Section: Discussionmentioning

confidence: 99%

High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via the TLR4/NF-kB Signaling Pathway

Liu

Xiong

et al. 2017

Am J Nephrol

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“…TLR4/NF-κB pathway appears to play a critical role in the pathogenesis with a variety of inflammatory conditions [ 32 ]. The proinflammatory role of TLR4/NF-κB pathway has been demonstrated to be involved in the progression of diabetes and diabetic complication [ 33 , 34 ]. Upon stimulation, activation of TLR4 pathway subsequently activated the NF-κB pathway and triggered NF-κB-dependent inflammatory response, which might ultimately aggravate renal dysfunction in acute and chronic kidney diseases [ 35 , 36 ].…”

Section: Discussionmentioning

confidence: 99%

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway

et al. 2018

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BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal failure, contributing to severe morbidity and mortality in diabetic patients. Berberine (BBR) has been well characterized to exert renoprotective effects in DN progression. However, the action mechanism of BBR in DN remains to be fully understood.MethodsThe DN rat model was generated by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) while 30 mM high glucose (HG)-treated podocytes were used as an in vitro DN model. The fasting blood glucose level and ratio of kidney weight to body weight were measured after BBR treatment (50, 100, or 200 mg/kg) in STZ-induced DN rats. The renal injury parameters including 24-h urinary protein, blood urea nitrogen and serum creatinine were assessed. qRT-PCR was performed to detect the transcript amounts of inflammatory factors. The concentrations of inflammatory factors were evaluated by ELISA kits. Western blot analysis was conducted to measure the amounts of TLR4/NF-κB-related proteins. The apoptotic rate of podocytes was analyzed by flow cytometry using Annexin V/propidium iodide.ResultsBerberine reduced renal injury in STZ-induced DN rat model, as evidenced by the decrease in fasting blood glucose, ratio of kidney weight to body weight, 24-h urinary protein, serum creatinine, and blood urine nitrogen. BBR attenuated the systemic and renal cortex inflammatory response and inhibited TLR4/NF-κB pathway in STZ-induced DN rats and HG-induced podocytes. Also, HG-induced apoptosis of podocytes was lowered by BBR administration. Furthermore, blockade of TLR4/NF-κB pathway by resatorvid (TAK-242) or pyrrolidine dithiocarbamate aggravated the inhibitory effect of BBR on HG-induced inflammatory response and apoptosis in podocytes.ConclusionsBerberine ameliorated DN through relieving STZ-induced renal injury, inflammatory response, and podocyte HG-induced apoptosis via inactivating TLR4/NF-κB pathway.

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“…CK2α, a crucial kinase involved in inflammation and cell proliferation, mediates activation of NF-κB by interacting with IκBα in HG-treated GMCs, which is a novel and important way for regulation on DN [ 21 ]. For investigating the regulatory mechanism between SphK1 and CK2α, activation of NF-κB was measured in GMCs including NF-κB nuclear translocation, transcriptional activity and DNA binding activity after overexpression of exogenous CK2α while expression of SphK1 was knocked down by siRNA.…”

Section: Discussionmentioning

confidence: 99%

“…What’s more, CK2α participates in development and progression of diseases including angiogenesis, glomerulonephritis, organogenesis and cancer [ 17 – 20 ]. Our previous study shows that activated CK2α provokes inflammatory nuclear factor NF-κB through interacting with IκB to increase its degradation, upregulating expressions of inflammatory fibrotic factors including FN and ICAM-1 under diabetic state [ 21 ].…”

Section: Introductionmentioning

confidence: 99%

Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-κB signaling pathway: involvement of CK2α

Huang

Chen

et al. 2017

Oncotarget

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Sphingosine kinase 1 (SphK1) plays a pivotal role in regulating diabetic renal fibrotic factors such as fibronectin (FN) and intercellular adhesion molecule-1 (ICAM-1). Especially, activation of SphK1 is closely linked to the body inflammatory reaction. Casein kinase 2α subunit (CK2α), a protein kinase related to inflammatory reaction, influences diabetic renal fibrosis and expressions of FN and ICAM-1 via NF-κB pathway. However, the mechanism by which SphK1 mediates diabetic renal fibrosis has not yet fully elucidated. The current study is aimed to investigate if SphK1 mediates diabetic renal fibrotic pathological process via inflammatory pathway and activation of CK2α. The following findings were observed: (1) Expressions of SphK1 were upregulated in kidneys of diabetic mice and rats; (2) Knockdown of SphK1 expression suppressed high glucose (HG)-induced NF-κB nuclear translocation and expressions of FN and ICAM-1; (3) Compared with C57 diabetic mice, SphK1-/- diabetic mice exhibited less renal fibrotic lesions, FN accumulation and NF-κB nuclear accumulation in glomeruli of kidneys; (4) SphK1 mediated phosphorylation of CK2α, while CK2α knockdown depressed SphK1-induced activation of NF-κB pathway. This study indicates the essential role of SphK1 in regulating activation of CK2α and diabetic renal fibrotic pathological process via NF-κB.

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Protein kinase CK2α catalytic subunit ameliorates diabetic renal inflammatory fibrosis via NF-κB signaling pathway

Cited by 30 publications

References 44 publications

High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via the TLR4/NF-kB Signaling Pathway

High Uric Acid-Induced Epithelial-Mesenchymal Transition of Renal Tubular Epithelial Cells via the TLR4/NF-kB Signaling Pathway

Berberine ameliorates diabetic nephropathy by inhibiting TLR4/NF-κB pathway

Sphingosine kinase 1 mediates diabetic renal fibrosis via NF-κB signaling pathway: involvement of CK2α

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