21 research outputs found
Table2_Hydrogen sulfide alleviates uremic cardiomyopathy by regulating PI3K/PKB/mTOR-mediated overactive autophagy in 5/6 nephrectomy mice.XLSX
The gasotransmitter hydrogen sulfide (H2S) plays important physiological and pathological roles in the cardiovascular system. However, the involvement of H2S in recovery from uremic cardiomyopathy (UCM) remains unclear. This study aimed to determine the therapeutic efficacy and elucidate the underlying mechanisms of H2S in UCM. A UCM model was established by 5/6 nephrectomy in 10-week-old C57BL/6 mice. Mice were treated with sodium hydrosulfide (NaHS, H2S donor), L-cysteine [L-Cys, cystathionine gamma-lyase (CSE) substrate], and propargylglycine (PPG, CSE inhibitor). Treatment of H9C2 cardiomyocytes utilized different concentrations of uremic serum, NaHS, PPG, and PI3K inhibitors (LY294002). Mouse heart function was assessed by echocardiography. Pathological changes in mouse myocardial tissue were identified using hematoxylin and eosin and Masson’s trichrome staining. Cell viability was assessed using the Cell Counting Kit-8. The protein expressions of CSE, p-PI3K, PI3K, p-PKB, PKB, p-mTOR, mTOR, and autophagy-related markers (Beclin-1, P62, and LC3) were detected using Western blotting. We found that NaHS and L-Cys treatment attenuated myocardial disarray, fibrosis, and left ventricular dysfunction in UCM mice. These abnormalities were further aggravated by PPG supplementation. Enhanced autophagy and decreased phosphorylation of PI3K, PKB, and mTOR protein expression by UCM were altered by NaHS and L-Cys treatment. In vitro, uremic serum increased overactive autophagy and decreased the phosphorylation levels of PI3K, PKB, and mTOR in cardiomyocytes, which was substantially exacerbated by endogenous H2S deficiency and attenuated by pre-treatment with 100 µm NaHS. However, the protective effects of NaHS were completely inhibited by LY294002. These findings support a protective effect of H2S exerted against UCM by reducing overactive autophagy through activation of the PI3K/PKB/mTOR pathway.</p
Image_5_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.TIF
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Table_5_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.XLS
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Table_4_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.XLS
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Image_7_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.TIF
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Image_4_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.TIF
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Table_6_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.XLS
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
DataSheet1_Hydrogen sulfide alleviates uremic cardiomyopathy by regulating PI3K/PKB/mTOR-mediated overactive autophagy in 5/6 nephrectomy mice.PDF
The gasotransmitter hydrogen sulfide (H2S) plays important physiological and pathological roles in the cardiovascular system. However, the involvement of H2S in recovery from uremic cardiomyopathy (UCM) remains unclear. This study aimed to determine the therapeutic efficacy and elucidate the underlying mechanisms of H2S in UCM. A UCM model was established by 5/6 nephrectomy in 10-week-old C57BL/6 mice. Mice were treated with sodium hydrosulfide (NaHS, H2S donor), L-cysteine [L-Cys, cystathionine gamma-lyase (CSE) substrate], and propargylglycine (PPG, CSE inhibitor). Treatment of H9C2 cardiomyocytes utilized different concentrations of uremic serum, NaHS, PPG, and PI3K inhibitors (LY294002). Mouse heart function was assessed by echocardiography. Pathological changes in mouse myocardial tissue were identified using hematoxylin and eosin and Masson’s trichrome staining. Cell viability was assessed using the Cell Counting Kit-8. The protein expressions of CSE, p-PI3K, PI3K, p-PKB, PKB, p-mTOR, mTOR, and autophagy-related markers (Beclin-1, P62, and LC3) were detected using Western blotting. We found that NaHS and L-Cys treatment attenuated myocardial disarray, fibrosis, and left ventricular dysfunction in UCM mice. These abnormalities were further aggravated by PPG supplementation. Enhanced autophagy and decreased phosphorylation of PI3K, PKB, and mTOR protein expression by UCM were altered by NaHS and L-Cys treatment. In vitro, uremic serum increased overactive autophagy and decreased the phosphorylation levels of PI3K, PKB, and mTOR in cardiomyocytes, which was substantially exacerbated by endogenous H2S deficiency and attenuated by pre-treatment with 100 µm NaHS. However, the protective effects of NaHS were completely inhibited by LY294002. These findings support a protective effect of H2S exerted against UCM by reducing overactive autophagy through activation of the PI3K/PKB/mTOR pathway.</p
Image_6_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.TIF
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p
Table_1_Common gene signatures and molecular mechanisms of diabetic nephropathy and metabolic syndrome.XLS
BackgroundDiabetic nephropathy (DN) is the leading cause of end-stage renal disease. Multiple metabolic toxicities, redox stress, and endothelial dysfunction contribute to the development of diabetic glomerulosclerosis and DN. Metabolic syndrome (MetS) is a pathological state in which the body’s ability to process carbohydrates, fats, and proteins is compromised because of metabolic disorders, resulting in redox stress and renal remodeling. However, a causal relationship between MetS and DN has not been proven. This study aimed to provide valuable information for the clinical diagnosis and treatment of MetS with DN.MethodsHere, transcriptome data of DN and MetS patients were obtained from the Gene Expression Omnibus database, and seven potential biomarkers were screened using bioinformatics analysis. In addition, the relationship between these marker genes and metabolism and immune infiltration was explored. Among the identified marker genes, the relationship between PLEKHA1 and the cellular process, oxidative phosphorylation (OXPHOS), in DN was further investigated through single-cell analysis.ResultsWe found that PLEKHA1 may represent an important biomarker that perhaps initiates DN by activating B cells, proximal tubular cells, distal tubular cells, macrophages, and endothelial cells, thereby inducing OXPHOS in renal monocytes.ConclusionOverall, our findings can aid in further investigation of the effects of drug treatment on single cells of patients with diabetes to validate PLEKHA1 as a therapeutic target and to inform the development of targeted therapies.</p