Epidermal Growth Factor Protects Against High Glucose-Induced Podocyte Injury Possibly via Modulation of Autophagy and PI3K/AKT/mTOR Signaling Pathway Through DNA Methylation

Sun, Yunyan; Deng, Ming; Ke, Xiao Xue; Lei, Xiangyang; Ju, Hao; Liu, Zhiming

doi:10.2147/dmso.s299562

Cited by 15 publications

(6 citation statements)

References 59 publications

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“… 38 The EGF was found to protect against high glucose-induced podocyte injury by promoting podocyte proliferation and inhibiting podocyte apoptosis. 39 Exogenous EGF accelerates the regeneration of kidney tubules and the recovery of kidney function in animal models of acute kidney injury. 40 As such, EGF might play a protective role in the reduction of proteinuria by repairing podocytes and tubular cells.…”

Section: Discussionmentioning

confidence: 99%

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy

et al. 2023

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Background This study investigated the association between urinary epidermal growth factor (EGF) and complete remission (CR) of proteinuria in children with IgA nephropathy (IgAN). Methods We included 108 patients from the Registry of IgA Nephropathy in Chinese Children. The urinary EGF at the baseline and follow-up were measured and normalized by urine creatinine (expressed as uEGF/Cr). The person-specific uEGF/Cr slopes were estimated using linear mixed-effects models for the subset of patients with longitudinal data of uEGF/Cr. Cox models were used to analyze the associations of baseline uEGF/Cr and uEGF/Cr slope with CR of proteinuria. Results Patients with high baseline uEGF/Cr were more likely to achieve CR of proteinuria (adjusted HR 2.24, 95% CI: 1.05–4.79). The addition of high baseline uEGF/Cr on the traditional parameters significantly improved the model fit for predicting CR of proteinuria. In the subset of patients with longitudinal data of uEGF/Cr, high uEGF/Cr slope was associated with a higher likelihood of CR of proteinuria (adjusted HR 4.03, 95% CI: 1.02–15.88). Conclusions Urinary EGF may be a useful noninvasive biomarker for predicting and monitoring CR of proteinuria in children with IgAN. Impact High levels of baseline uEGF/Cr (>21.45 ng/mg) could serve as an independent predictor for CR of proteinuria. The addition of baseline uEGF/Cr on the traditional clinical pathological parameters significantly improved the fitting ability for the prediction of CR of proteinuria. Longitudinal data of uEGF/Cr were also independently associated with CR of proteinuria. Our study provides evidence that urinary EGF may be a useful noninvasive biomarker in the prediction of CR of proteinuria as well as monitoring therapeutic response, thus guiding treatment strategies in clinical practice for children with IgAN.

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Section: Discussionmentioning

confidence: 99%

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy

et al. 2023

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“…Therefore, we focused on the role of necroptosis in diabetic nephropathy (DN) and identified EGF, PAG1, and ZFP36 as potential biomarkers associated with necroptosis using the WGCNA algorithm. EGF is mainly generated from the loop of Henle and the renal distal convoluted tubule, and a previous study suggested that EGF may protect against HG-induced podocyte injury by regulating autophagy, promoting cell proliferation, and inhibiting apoptosis [ 29 ]. Tenascin-C exerts a direct stimulatory effect on the epidermal growth factor (EGF) receptor signaling pathway within muscle stem cells.…”

Section: Discussionmentioning

confidence: 99%

Investigating EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy: an in silico and in vitro validation study

Wang,

Zhang,

Peng

2023

Aging

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The current study aims to understand the mechanisms behind regulated cell death (RCD) in diabetic nephropathy and identify related biomarkers through bioinformatics and experimental validation. Datasets of bulk and single-cell RNA sequencing were obtained from public databases and analyzed using gene set variation analysis (GSVA) with gene sets related to RCD, including autophagy, necroptosis, pyroptosis, apoptosis, and ferroptosis. RCD-related gene biomarkers were identified using weighted gene correlation network analysis (WGCNA). The results were verified through experiments with an independent cohort and in vitro experiments. The GSVA revealed higher necroptosis scores in diabetic nephropathy. Three necroptosis-related biomarkers, EGF, PAG1, and ZFP36, were identified and showed strong diagnostic ability for diabetic kidney disease. In vitro experiments showed high levels of necroptotic markers in HK-2 cells treated with high glucose. Bioinformatics and experimental validation have thus identified EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy.

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“…In proliferative LN, immune complex deposition leads to glomerular visceral epithelial cells (podocytes) damage and proteinuria. Recently, EGF has been shown to promote podocyte proliferation and re-expression of differentiation markers after exposure to high glucose concentrations [ 40 ]. Therefore, EGF could decrease proteinuria in LN by restoring glomerular function through its ability to repair podocytes.…”

Section: Discussionmentioning

confidence: 99%

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios

et al. 2022

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Introduction There is a need for sensitive and specific biomarkers to predict kidney damage and therapeutic response in lupus nephritis (LN). Monocyte chemoattractant protein-1 (MCP-1) and epidermal growth factor (EGF) are cytokines with divergent roles. EGF or EGF/MCP1 ratio have been shown to correlate with prognosis in primary glomerulonephritis, but there is limited information in lupus nephritis (LN). This study evaluated the roles of MCP-1, EGF or their ratio as biomarkers of histopathology and response to treatment in LN. Methods This was a cross-sectional and observational study. Baseline urine MCP-1 and EGF levels in systemic lupus erythematosus (SLE) patients and controls (total n = 101) were compared, and levels were correlated with clinicopathological findings and subsequent response to treatment. Results MCP-1 was higher in active LN (n = 69) compared to other SLE groups and controls, whereas EGF was not different. MCP-1 correlated with disease activity (proteinuria, renal SLEDAI, classes III/IV/V, and high activity index.) By contrast, EGF correlated with eGFR, but not with proteinuria, activity index, or class III/IV/V. MCP-1 was higher, and EGF was lower in high chronicity index. EGF/MCP-1 decreased with greater clinicopathological severity. In a subgroup with proliferative LN who completed six months of induction therapy (n = 41), EGF at baseline was lower in non-responders compared to responders, whereas MCP-1 was similar. By multivariable analysis, baseline EGF was independently associated with subsequent treatment response. Area under the curve for EGF to predict response was 0.80 (0.66–0.95). EGF ≥ 65.6 ng/ mgCr demonstrated 85% sensitivity and 71% specificity for response. EGF/MCP-1 did not improve the prediction for response compared to EGF alone. Conclusion MCP-1 increased with disease activity, whereas EGF decreased with low GFR and chronic damage. Urine EGF may be a promising biomarker to predict therapeutic response in LN. EGF/MCP-1 did not improve the prediction of response.

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Epidermal Growth Factor Protects Against High Glucose-Induced Podocyte Injury Possibly via Modulation of Autophagy and PI3K/AKT/mTOR Signaling Pathway Through DNA Methylation

Cited by 15 publications

References 59 publications

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy

Urinary epidermal growth factor predicts complete remission of proteinuria in Chinese children with IgA nephropathy

Investigating EGF and PAG1 as necroptosis-related biomarkers for diabetic nephropathy: an in silico and in vitro validation study

Predicting treatment response and clinicopathological findings in lupus nephritis with urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratios

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