Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through <i>c‐Myc</i>, DNMT1 and EZH2

Xie, Lin; Ma, Shengchao; Ding, Ning; Wang, Yanhua; Lu, Guanjun; Xu, Lingbo; Wang, Qingqing; Liu, Kun; Jie, Yuzheng; Zhang, Hui; Ai, Yang; Gao, Yujing; Zhang, Huiping; Jiang, Yideng

doi:10.1002/1878-0261.13032

Cited by 8 publications

(3 citation statements)

References 30 publications

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“…HHcy has also been reported to be associated with acceleration of CKD progression. The relevant study demonstrated that Hcy promotes podocytes apoptosis through regulation of the epigenetic modifiers DNA methyltransferase 1 (DNMT1) and enhancer of zeste homolog 2 (EZH2), which are recruited by c-Myc to miR-1929-5p promoter and silence miR-1929-5p expression [ 48 ] ( Figure 3 ). Hcy also had a role in the development of acute kidney injury in cbs +/− mice.…”

Section: Methionine and Its Metabolite Homocysteinementioning

confidence: 99%

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

Luo-kun

Zhang

et al. 2022

Nutrients

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Diabetic kidney disease (DKD) occurs in 25–40% of patients with diabetes. Individuals with DKD are at a significant risk of progression to end-stage kidney disease morbidity and mortality. At present, although renal function-decline can be retarded by intensive glucose lowering and strict blood pressure control, these current treatments have shown no beneficial impact on preventing progression to kidney failure. Recently, in addition to control of blood sugar and pressure, a dietary approach has been recommended for management of DKD. Amino acids (AAs) are both biomarkers and causal factors of DKD progression. AA homeostasis contributes to renal hemodynamic response and glomerular hyperfiltration alteration in diabetic patients. This review discusses the links between progressive kidney dysfunction and the metabolic homeostasis of histidine, tryptophan, methionine, glutamine, tyrosine, and branched-chain AAs. In addition, we emphasize the regulation effects of special metabolites on DKD progression, with a focus on causality and potential mechanisms. This paper may offer an optimized protein diet strategy with concomitant management of AA homeostasis to reduce the risks of DKD in a setting of hyperglycemia.

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Section: Methionine and Its Metabolite Homocysteinementioning

confidence: 99%

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

Luo-kun

Zhang

et al. 2022

Nutrients

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“…Under the interaction of DNMT1 and HMT G9a, homocysteine inhibits the expression of reticulo-oxidoreductase 1α (ERO1α), activates the occurrence of endoplasmic reticulum stress and hepatocyte apoptosis, causing liver injury [ 152 ]. In addition, DNA methylases are also involved in the progression of chronic kidney disease to renal cell carcinoma [ 153 ].…”

Section: Types Of Chromatin Modifiersmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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“…Excessive apoptosis may lead to disease. Lin Xie found that homocysteine promotes podocyte apoptosis by regulating epigenetic modifiers DNMT1 and EZH2, which is accompanied by glomerular damage, leading to the progress of CKD ( Xie et al, 2021 ). Nan Yu found that podocytes are an important part of renal glomerular filtration barrier, and podocyte dysfunction and apoptosis are important factors leading to the progress of chronic kidney disease (CKD) ( Yu et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

The expression of apoptosis related genes in HK-2 cells overexpressing PPM1K was determined by RNA-seq analysis

et al. 2022

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Chronic kidney disease (CKD) is a serious disease that endangers human health. It is reported that inhibiting renal cell apoptosis can delay the progress of CKD. Our previous study found that the mice with protein phosphatase Mg2+/Mn2+ dependent 1K (PPM1K) gene deletion had obvious symptoms of glomerular vascular and interstitial vascular dilatation, congestion and hemorrhage, glomerular hemorrhage and necrosis, interstitial fibrous tissue proliferation, decreased urinary creatinine clearance, and increased urinary protein level. In addition, studies have found that PPM1K is essential for cell survival, apoptosis and metabolism. However, no study has confirmed that PPM1K can inhibit renal cell apoptosis. In this study, PPM1K was overexpressed in human kidney-2 cells (HK-2), and the biological process of differentially expressed genes and its effect on apoptosis were comprehensively screened by RNA sequencing (RNA-seq). Through sequencing analysis, we found that there were 796 differentially expressed genes in human renal tubular epithelial cells transfected with PPM1K gene, of which 553 were down-regulated and 243 were up-regulated. Enrichment analysis found that differentially expressed genes may play an important role in amino acid metabolism and biosynthesis. In the GO analysis functional pathway list, we also found that multiple genes can be enriched in apoptosis related pathways, such as G0S2, GADD45A, TRIB3, VEGFA, NUPR1 and other up-regulated genes, and IL-6, MAGED1, CCL2, TP53INP1 and other down-regulated genes. Then we verified these differentially expressed genes by RT-PCR, and found that only the RT-PCR results of G0S2, VEGFA and NUPR1 were consistent with the transcriptome sequencing results. We believe that G0S2, VEGFA, NUPR1 and other genes may participate in the apoptosis process of HK-2 cells induced by PPM1K.In conclusion, these findings provide some data support for the study of HK-2 cell apoptosis mechanism, and also provide a scientific theoretical basis for further study of the effect of PPM1K on kidney disease.

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Homocysteine induces podocyte apoptosis by regulating miR‐1929‐5p expression through c‐Myc, DNMT1 and EZH2

Cited by 8 publications

References 30 publications

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

Metabolic Homeostasis of Amino Acids and Diabetic Kidney Disease

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

The expression of apoptosis related genes in HK-2 cells overexpressing PPM1K was determined by RNA-seq analysis

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