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RNA Sequencing of Cardiac in STZ-induced Rat model Uncovers Potential Target of Diabetic cardiomyopathy

ABSTRACT: Diabetic cardiomyopathy (DCM) is one of the major causes of heart failure in diabetic patients, but its pathogenesis remains unclear. Long non-coding RNAs (lncRNAs) are involved in the development of various cardiovascular diseases, but is little known in DCM. We build diabetic cardiomyopathy (DCM) rat model and investigated the genome-wide expression profiling of cardiac lncRNAs and mRNAs in rat model with and without DCM by RNA sequencing, to uncovers potential path mechanisms target of DCM.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE197999 | GEO | 2022/03/13

REPOSITORIES: GEO

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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.

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RNA Sequencing of Cardiac in STZ-induced Rat model Uncovers Potential Target of Diabetic cardiomyopathy

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