NF-κB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in glomerulonephritis

Zhang, Hongxia; Mao, Xing; Sun, Yu; Hu, Ruimin; Luo, Weili; Zhao, Zhonghua; Chen, Qi; Zhang, Zhigang

doi:10.3892/mmr.2015.3780

Cited by 23 publications

(12 citation statements)

References 36 publications

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“…Liu et al [ 61 ] found that curcumin could prevent glomerular podocyte injury by inhibiting activated Wnt family members and β -catenin downstream effectors in obesity-related glomerular disease model. Zhang et al [ 62 , 63 ] demonstrated that ubiquitin carboxy-terminal hydrolase-1 (UCH-L1) is abnormally expressed in injury podocytes, especially in immune-mediated disease. They also proved that the Wnt/ β -catenin signal pathway is promptly activated in podocyte, coinciding with overexpression of UCH-L1 induced by high glucose meanwhile [ 64 ].…”

Section: Main Signaling Pathways Of Podocyte Injury Mechanism In Dmentioning

confidence: 99%

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Dai

Liu

2017

Journal of Diabetes Research

208

139

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Diabetic nephropathy (DN) together with glomerular hyperfiltration has been implicated in the development of diabetic microangiopathy in the initial stage of diabetic diseases. Increased amounts of urinary protein in DN may be associated with functional and morphological alterations of podocyte, mainly including podocyte hypertrophy, epithelial-mesenchymal transdifferentiation (EMT), podocyte detachment, and podocyte apoptosis. Accumulating studies have revealed that disruption in multiple renal signaling pathways had been critical in the progression of these pathological damages, such as adenosine monophosphate-activated kinase signaling pathways (AMPK), wnt/β-catenin signaling pathways, endoplasmic reticulum stress-related signaling pathways, mammalian target of rapamycin (mTOR)/autophagy pathway, and Rho GTPases. In this review, we highlight new molecular insights underlying podocyte injury in the progression of DN, which offer new therapeutic targets to develop important renoprotective treatments for DN over the next decade.

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Section: Main Signaling Pathways Of Podocyte Injury Mechanism In Dmentioning

confidence: 99%

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Dai

Liu

2017

Journal of Diabetes Research

208

139

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“…52 Another group also found enhanced NF-kB activity in podocytes and other glomerular cells in biopsy specimens from patients with lupus nephritis and IgA nephropathy and patients with nonproliferative membranous nephropathy compared with healthy controls. 53 More direct evidence of podocyte activity was indicated in a study that found that podocyte-specific NEMOdeficient mice have faster recovery from anti-GBMe mediated glomerular injury. 12 Glomerular expression of inflammatory chemokines (CCL2, CCL5, and CCL7) was also reduced in NEMO-deficient mice.…”

Section: Discussionmentioning

confidence: 99%

ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation

Korte

Caster

Barati

et al. 2017

The American Journal of Pathology

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Transcription factor NF-κB regulates expression of numerous genes that control inflammation and is activated in glomerular cells in glomerulonephritis (GN). We previously identified genetic variants for a NF-κB regulatory, ubiquitin-binding protein ABIN1 as risk factors for GN in systemic autoimmunity. The goal was to define glomerular inflammatory events controlled by ABIN1 function in GN. Nephrotoxic serum nephritis was induced in wild-type (WT) and ubiquitin-binding deficient ABIN1[D485N] mice, and renal pathophysiology and glomerular inflammatory phenotypes were assessed. Proteinuria was also measured in ABIN1[D485N] mice transplanted with WT mouse bone marrow. Inflammatory activation of ABIN1[D472N] (D485N homolog) cultured human-derived podocytes, and interaction with primary human neutrophils were also assessed. Disruption of ABIN1 function exacerbated proteinuria, podocyte injury, glomerular NF-κB activity, glomerular expression of inflammatory mediators, and glomerular recruitment and retention of neutrophils in antibody-mediated nephritis. Transplantation of WT bone marrow did not prevent the increased proteinuria in ABIN1[D845N] mice. Tumor necrosis factor-stimulated enhanced expression and secretion of NF-κB-targeted proinflammatory mediators in ABIN1[D472N] cultured podocytes compared with WT cells. Supernatants from ABIN1[D472N] podocytes accelerated chemotaxis of human neutrophils, and ABIN1[D472N] podocytes displayed a greater susceptibility to injurious morphologic findings induced by neutrophil granule contents. These studies define a novel role for ABIN1 dysfunction and NF-κB in mediating GN through proinflammatory activation of podocytes.

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“…Our earlier work had proved that UCH-L1 is expressed aberrantly in the injured podocytes of many nephrites, especially the immunocomplex-mediated nephrites [ 20 , 21 ]. Podocyte injuries are closely related to DN [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Wnt/β-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy

Zhang

Luo

Sun

et al. 2016

IJMS

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Increasing studies identified podocyte injury as a key early risk factor resulting in diabetic nephropathy (DN). The ubiquitin carboxy-terminal hydrolase 1 (UCH-L1) participates in podocyte differentiation and injury, which is elevated in the podocytes of a variety of nephritis. Whether UCH-L1 expression is positively related to podocyte injury of DN remains unclear. In this study, elevated expression of UCH-L1 and its intrinsic mechanism in high glucose (HG)-stimulated murine podocytes were investigated using western blot and real-time quantitative PCR. Kidney biopsies of DN patients and health individuals were stained by immunofluorescence (IF) method. The morphological and functional changes of podocytes were tested by F-actin staining and cell migration assay. Results demonstrated that HG induced upregulation of UCH-L1 and activation of the Wnt/β-catenin signaling pathway in podocytes. However, blocking of the Wnt pathway by dickkopf related protein 1 (DKK1) eliminated the above changes. Furthermore, IF staining confirmed that, compared with healthy individuals, the expression of UCH-L1 and β-catenin were obviously increased in kidney biopsy of DN patients. Overexpression of UCH-L1 remodeled its actin cytoskeleton, increased its cell migration and impacted its important proteins. All the findings manifested that Wnt/β-catenin/UCH-L1 may be a new potential therapy method in the treatment of DN in future.

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NF-κB upregulates ubiquitin C-terminal hydrolase 1 in diseased podocytes in glomerulonephritis

Cited by 23 publications

References 36 publications

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

Research Progress on Mechanism of Podocyte Depletion in Diabetic Nephropathy

ABIN1 Determines Severity of Glomerulonephritis via Activation of Intrinsic Glomerular Inflammation

Wnt/β-Catenin Signaling Mediated-UCH-L1 Expression in Podocytes of Diabetic Nephropathy

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