Role of lactylation in diabetic nephropathy: based on LC‒MS/MS analysis
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus Musculus
SUBMITTER: 
Zhangsuo Liu
PROVIDER: PXD050070 | iProX | Fri Feb 23 00:00:00 GMT 2024
REPOSITORIES: iProX
Similar Datasets
Project description:Lysine lactylation (Kla), is a newly found post-translational modification that has been found to be involved in the pathogenesis of many diseases. However, the specific effect of protein lactylation has not been reported on the development of diabetic cardiomyopathy (DCM). Here, the purpose of this study was determined whether protein lactylation was involved in the progression of DCM. LC-MS/MS was used to perform proteomic and lactate analysis on the heart tissues of db/m mice (Control group) and db/db mice (DCM group). Subsequently, a series of bioinformatics analyses were used to analyze the kla site and Kla modified proteins in two groups, including GO enrichment, KEGG enrichment, LASSO regression, Logistic regression, random forest (RF), VM-Recursive Feature Elimination (SVM-RFE) algorithm, and other analysis methods. The bioinformatics data analysis showed that the Kla sites in the DCM group were more than those in the Control group. In addition, subcellular localization analysis showed that Kla modified proteins were mainly located in mitochondria and cytoplasm. The protein lactylated modification mainly occurred on histone H2, and compared with the Control group, the modification of H4C1-K32 sites was significantly higher in the DCM group. Furthermore, there were 113 significantly modified kla sites corresponding to 78 modified proteins in the DCM group, while there were 37 significantly modified kla sites corresponding to 25 modified proteins in the Control group. These Kla modified proteins were involved in biological processes and pathways related to glucose metabolism and DCM. Finally, five kla sites were selected as candidate sites by using four machine learning methods, namely A2ASS6 _ K928 _ Ttn, A2ASS6 _ K13499 _ Ttn, Q61425 _ K212 _ Hadh, Q8K2B3 _ K517 _ Sdha, and Q9R0Y5 _ K100 _ Ak1. In conclusions, the present study first reported on the combination of lactylome and proteome of DCM, providing a reliable basis for further investigating the roles of Kla and Kla modified proteins in DCM.
2026-05-25 | PXD067368 | Pride
Project description:diabetes, mouse models, diabetic nephropathy, streptozotocin db/db Keywords: other
2004-01-20 | GSE710 | GEO
Project description:The present study aims to evaluate the alterations induced by type I diabetes and the associated hyperglycemia on the proteome of renal tissue using a transgenic experimental animal model. Diabetic and non-diabetic kidney samples were analyzed by liquid nano-chromatography mass spectrometry and protein abundance was evaluated bylabel free quantification.
2020-09-24 | PXD018053 | Pride
Project description:To extensively elucidate protein lactylation (Kla), a proteome-wide analysis of lactylation was carried out in Staphylococcus aureus. Proteins extracted from Staphylococcus aureus were digested by trypsin and anti-lactyl lysine antibody was used to enrich the lactylated peptides, which were determined by following LC-MS/MS analysis.
2024-10-08 | PXD046022 | Pride
Project description:Persistently enhancement of glycolytic activity has been increasingly implicated as a key contributor to the development of diabetic kidney disease (DKD). Lactate, the end product of glycolysis, can trigger histone lactylation, —an emerging epigenetic modification involved in regulating gene expression, yet its functional significance in DKD remains largely unclear. Here, we observed that 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3), a key glycolytic enzyme, was remarkably induced in tubular epithelial cells (TECs) in both DKD patients and mice model. Inhibition the expression of PFKFB3 mitigated kidney fibrosis, and preserved kidney function in DKD mice model. Conversely, upregulation of PFKFB3 aggravates renal fibrogenesis and promotes the deterioration of renal pathology. Moreover, we demonstrated that reducing the lactate levels markedly alleviated renal fibrosis in DKD. Mechanistically, lactate generated via PFKFB3-driven glycolytic reprogramming selectively enhances H4K12 lactylation at the HIPK2 promoter, thereby activating its transcription and driving renal fibrotic progression. These findings suggest that tubular PFKFB3 enhancing HIPK2 expression by promoting H4K12la-mediated gene transcription. Thus, targeting the PFKFB3-mediated HIPK2 activation in renal tubular cells could be a novel strategy for DKD.
2026-04-22 | GSE328635 | GEO
Project description:This study employed RNA-seq to profile the transcriptomic changes in the renal cortex of diabetic nephropathy (DN) mouse models and to investigate the regulatory effects of the traditional Chinese medicine formula Yiqi Huoxue Yangyin Decoction (YHY). Kidney cortex tissues were collected from diabetic db/db mice and non-diabetic db/m control mice. Db/db mice were further divided into two groups: one treated with YHY and one vehicle-treated. Each group contained biological replicates (n=4).* Total RNA was extracted, and paired-end sequencing was performed on the Illumina NovaSeq 6000 platform. Differential gene expression analysis was conducted to identify genes and pathways altered by diabetes and modulated by YHY treatmen
2026-05-15 | GSE315612 | GEO
Project description: Not available
| S-EPMC4660682 | biostudies-literature
Project description:Gene expression profiling in glomeruli from human kidneys with diabetic nephropathy Keywords = Diabetes Keywords = kidney Keywords = glomeruli Keywords: other
2004-04-01 | GSE1009 | GEO
Project description:Aim: To compare transcriptomic profiles of kidney cortex between healthy db/m mice, and mice with early stage diabetic kidney disease (uninephrectomized db/db injected with LacZAAV) and advanced stage diabetic kidney disease (uninephrectomized db/db mice injected with ReninAAV) Methods: Bulk RNA sequecing using the Illumina NextSeq 500 platform. Results: We identified 5,500 differentially expressed genes (DEGs) in db/db UNx LacZAVV mice compared to healthy controls, and 4,470 DEGs were identified in db/db UNx ReninAAV mice compared to healthy controls. Also, we showed in supplementery files that 3,039 DEGs were identified between db/db UNx LacZAAV mice and db/db UNx ReninAAV mice. Conclusion: We identified several gene expression changes in our two animal models of diabetic kidney disease.
2021-10-24 | GSE185616 | GEO
Project description:Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with nondiabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network. Keywords: Dyslipidemia is a significant risk factor for progression of diabetic kidney disease (DKD). To identify individual lipids and lipid networks that may be involved in DKD progression, we performed untargeted lipidomic analysis of kidney cortex tissue from diabetic db/db and db/db eNOS-/- mice along with non-diabetic littermate controls. A subset of mice were treated with the renin-angiotensin system (RAS) inhibitors, lisinopril and losartan, which improves the DKD phenotype in the db/db eNOS-/- mouse model. Of the three independent variables in this study, diabetes had the largest impact on overall lipid levels in the kidney cortex, while eNOS expression and RAS inhibition had smaller impacts on kidney lipid levels. Kidney lipid network architecture, particularly of networks involving glycerolipids such as triacylglycerols, was substantially disrupted by worsening kidney disease in the db/db eNOS-/- mice compared to the db/db mice, a feature that was reversed with RAS inhibition. This was associated with decreased expression of the stearoyl-CoA desaturases, Scd1 and Scd2, with RAS inhibition. In addition to the known salutary effect of RAS inhibition on DKD progression, our results suggest a previously unrecognized role for RAS inhibition on the kidney triacylglycerol lipid metabolic network.
2022-07-08 | GSE141680 | GEO