Association of <i>EPHX2</i> R287Q Polymorphism with Diabetic Nephropathy in Chinese Type 2 Diabetic Patients

Ma, Liang; Yan, Meihua; Kong, Xiaomu; Jiang, Yongwei; Zhao, Tingting; Zhao, Hailing; Liu, Qian; Zhang, Haojun; Liu, Peng; Cao, Yongtong; Li, Ping

doi:10.1155/2018/2786470

Cited by 11 publications

(13 citation statements)

References 30 publications

(28 reference statements)

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“…They found that these SNPs are not associated with the increased risk of hypertension in the African American population (Dreisbach et al, 2005). Ma et al (2018) reported that the A allele of an exonic polymorphism in sEH rs751141 correlated with the incidence of DN in the Chinese T2D population negatively, which could be modulated by homocysteine level status.…”

Section: Association Of Seh Polymorphisms With Kidney-associated Disementioning

confidence: 99%

Inhibition of Soluble Epoxide Hydrolase for Renal Health

Liu

2019

Front. Pharmacol.

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A soluble epoxide hydrolase (sEH) mediates the metabolism of epoxy fatty acids to form the corresponding vicinal diols, which are usually inactive or less active than the epoxide substrates. The sEH enzyme presents in many organs, including but not limited to the liver, heart, spleen, lung, and kidney. Here we summarized the changes in the expression and activity of sEH in multiple renal diseases, such as acute kidney injury (AKI), diabetic nephrology (DN), chronic kidney diseases (CKD), hypertension-mediated renal damage, and other renal dysfunctions. We also discussed the pharmacologic effects and the underlying mechanisms of sEH inhibition by using an inhibitor of sEH and/or the generic deletion of sEH on multiple renal diseases. We believe that sEH is a potential therapeutic target for renal dysfunction although the target disease needs further investigation.

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Section: Association Of Seh Polymorphisms With Kidney-associated Disementioning

confidence: 99%

Inhibition of Soluble Epoxide Hydrolase for Renal Health

Liu

2019

Front. Pharmacol.

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“…It has been reported that the current standard therapy only achieves partial renoprotection, which greatly increases the need for novel and effective therapeutic approaches 4 . Evidence has demonstrated that DN usually occurs in familial clusters, highlighting the great significance of DN-related genetic factors in the development of DN and in the identification of more effective therapeutic strategies for DN 5 .…”

Section: Introductionmentioning

confidence: 99%

Silencing of long noncoding RNA PVT1 inhibits podocyte damage and apoptosis in diabetic nephropathy by upregulating FOXA1

Zhang

Liu

et al. 2019

Exp Mol Med

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The number of patients with diabetic nephropathy (DN) is still on the rise worldwide, and this requires the development of new therapeutic strategies. Recent reports have highlighted genetic factors in the treatment of DN. Herein, we aimed to study the roles of long noncoding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and histone 3 lysine 27 trimethylation (H3K27me3) in DN. A model of DN was established by inducing diabetes in mice with streptozotocin. Mouse podocyte clone 5 (MPC5) podocytes and primary podocytes were cultured in normal and high glucose media to observe cell morphology and to quantify PVT1 expression. The roles of PVT1 and enhancer of zeste homolog 2 (EZH2) were validated via loss-of-function and gain-of-function in vitro experiments to identify the interactions among PVT1, EZH2, and forkhead box A1 (FOXA1). The podocyte damage and apoptosis due to PVT1 and FOXA1 were verified with in vivo experiments. PVT1 was highly expressed in MPC5 and primary podocytes in DN patients and in cultures grown in high glucose medium. A large number of CpG (C-phosphate-G) island sites were predicted at the FOXA1 promoter region, where PVT1 recruited EZH2 to promote the recruitment of H3K27me3. The silencing of PVT1 or the overexpression of FOXA1 relieved the damage and inhibited the apoptosis of podocytes in DN, as was evidenced by the upregulated expression of synaptopodin and podocin, higher expression of Bcl-2, and lower expression of Bax and cleaved caspase-3. The key findings of this study collectively indicate that the suppression of lncRNA PVT1 exerts inhibitory effects on podocyte damage and apoptosis via FOXA1 in DN, which is of clinical significance.

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“…They also demonstrated that the AA genotype decreased risk of DN by 73% after adjustment for established DN risk factors. 23 The study done by Lee et al, revealed a significant effect of EPHX2 rs751141 on progression of IgA nephropathy (IgAN) in Korean population. They noticed better kidney survival in IgAN patients with the A allele, remarkable kidney vascular damage in patients with the G allele and higher in vivo activity of sEH in patients carrying the G allele.…”

Section: Discussionmentioning

confidence: 99%

“…20 However, a limited number of studies have examined this SNP in kidney disorders, 6,21,22 with only one study performed in diabetic kidney disease. 23 Considering the value of EETs in the kidney, we speculated that sequence variations within CYP2J2 and EPHX2 might have an impact on DN predisposition. In view of this, we designed this study to investigate the association of CYP2J2 rs2280275 and EPHX2 rs751141 with DN in Egyptian T2DM patients in relation to kidney function parameters.…”

Section: Introductionmentioning

confidence: 99%