Proteomic analysis revealed the altered kidney protein profile of a Cyld knockout mouse model

Zhao, Yanqing; Zhang, Y.; Song, Haibo; Wu, Fei; Wang, X. L.; Sun, Shisheng; Cui, Taixing; Tang, Dongqi

doi:10.4238/2015.june.1.14

Cited by 3 publications

(2 citation statements)

References 21 publications

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“…To the best of our knowledge, the present study is the first to use subcellular and functional proteomics to profile subcellular signaling in endothelial cells prior to, and following, PKC-β 2 activation. The proteomics analysis provided a detailed profile of these changes at the molecular level, and a number of the altered proteins identified were consistent with those of previous studies ( 54 – 56 ). The results of the present study demonstrated that PKC-β 2 may be an important molecular regulator of high glucose-induced functional and metabolic changes in HUVECs.…”

Section: Discussionsupporting

confidence: 85%

Subcellular proteomic approach for identifying the signaling effectors of protein kinase C-β2 under high glucose conditions in human umbilical vein endothelial cells

Zhang

Sun

Chen

et al. 2015

Molecular Medicine Reports

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The high glucose-induced activation of protein kinase C-β2 (PKC-β2) has an essential role in the pathophysiology of diabetes-associated vascular disease. In the present study, human umbilical vein endothelial cells (HUVECs) were cultured in high and normal glucose conditions prior to being infected with a recombinant adenovirus to induce the overexpression of PKC-β2. The activity of PKC-β2 was also decreased using a selective PKC-β2 inhibitor. A series of two-dimensional electrophoresis images detected ~800 spots in the nuclei, and ~600 spots in the cytosol. Following intra- and inter-group cross-matching, 38 significantly altered spots were identified as high glucose-induced and PKC-β2-associated nuclear proteins. In addition to the observation that the regulation of key proteins involved in the nuclear factor (NF)-κB signaling cascade occurred in the cytosol, various transcription factors, including peroxisome proliferator-activated receptor δ (PPAR-δ), were also altered in the nuclei. A human protein-protein interaction network of potential connections of PKC-β2-associated proteins was constructed in the proteomics investigation using Biological General Repository for Interaction Datasets. The results indicated that PKC-β2 may be involved in high glucose-induced glucose and lipid crosstalk by regulating PPAR-δ. In addition, NF-κB inhibitor-interacting Ras-like protein 1 may be important in the PKC-β2-NF-κB inhibitor-NF-κB signaling pathway in HUVECs under high-glucose conditions.

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Section: Discussionsupporting

confidence: 85%

Subcellular proteomic approach for identifying the signaling effectors of protein kinase C-β2 under high glucose conditions in human umbilical vein endothelial cells

Zhang

Sun

Chen

et al. 2015

Molecular Medicine Reports

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“…CYLD plays a protective role in tubulointerstitial inflammation in IgA nephropathy by a presumed regulation of the peroxisome proliferatoractivated receptor g pathway and is crucial for maintenance of renal function. 25 Expression as well as translation of CYLD was up-regulated after ASO treatment. CCND2 plays role in renal cell cycle and in the progression of diabetic nephropathy.…”

Section: Mir-182 Inhibition In Akimentioning

confidence: 94%

miR-182-5p Inhibition Ameliorates Ischemic Acute Kidney Injury

Wilflingseder

Jelencsics

Bergmeister

et al. 2017

The American Journal of Pathology

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Acute kidney injury (AKI) remains a major clinical event with high mortality rates. We previously identified renal miR-182 as the main driver of post-transplantation AKI. Therefore, we tested the causal inference of miR-182 by inhibiting its renal expression in vivo. In 45 rats AKI was induced by right nephrectomy and contralateral clamping of the renal pedicle for 40 minutes. Systemically administered antisense oligonucleotide (ASO) inhibited miR-182 in the kidneys up to 96 hours. The maximum creatinine elevation was on day 2 after injury (mg/dL; median and interquartile range): ASO 2.5mg/kg: 1.9 (1.3; 3.2), ASO 25mg/kg: 2.8 (0.7; 5.0), mismatch oligonucleotide (MM) 25mg/kg: 5.7 (5,0; 5.8), saline: 4.4 (3.5; 5.8) (P = 0.016, analysis of variance). Blinded semiquantitative histologic evaluation of renal biopsies showed better preserved morphology in both ASO groups than saline- and MM-treated kidneys (median and interquartile range of overall injury scores): ASO both concentrations 1 (1, 1), saline 3 (3, 3) and MM 3 (3, 3) (P< 0.001, analysis of variance). ASO facilitated cell proliferation, metabolism, and angiogenesis on a genome-wide level. ASO when applied in normothermic kidney machine perfusion reduced renal miR-182 expression by more than two magnitudes. In summary, we showed that in vivo inhibition of miR-182 by ASO improved kidney function and morphology after AKI. This technique may be applicable to reduce the high rate of AKI in the human renal transplantation setting.

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