Dataset Information

The Glomerulus Multi-Omics Analysis Provides Deeper Insights into Diabetic Nephropathy

ABSTRACT: Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD), however, the detail mechanisms remain unclear. Here, we integrated the transcriptomics and proteomics profiles of glomeruli isolated from 50 biopsy-proven DN patients and 25 controls to explore the new discoveries underlying the pathogenesis of DN. First, 1,152 genes were differentially expressed at mRNA or protein level, and 364 of them showed strong correlation. Those strong correlated genes were divided into four different functional modules, including energy metabolism processes, extracellular matrix organization and cell adhesion, mRNA metabolism and protein translation, immune system and inflammation. In addition, a transcription factors (TFs) - target genes (TGs) regulatory network was constructed, among which 30 TFs up-regulated at protein levels and 265 downstream TGs were differentially expressed at the mRNA levels. Those TFs constitute the integration centers of different signal transduction pathways, and have great therapeutic potential in controlling the abnormal expression of TGs and the pathological process of DN. Furthermore, 29 new DN-specific splice-junction peptides with high confidence were identified, which may exert novel roles in the pathological progression of DN. So, our in-depth integrative transcriptomic-proteomic analysis provided deeper insights into the pathogenesis of DN and opened the potential avenue for finding new therapeutic interventions in DN.

ORGANISM(S): Homo Sapiens

SUBMITTER: Zhihong Liu

PROVIDER: PXD040617 | iProX | Mon Mar 06 00:00:00 GMT 2023

REPOSITORIES: iProX

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Transcriptomics-proteomics Integration reveals alternative polyadenylation driving inflammation-related protein translation in patients with diabetic nephropathy.

Zhao Tingting T Zhan Dongdong D Qu Shuang S Jiang Song S Gan Wenhua W Qin Weisong W Zheng Chunxia C Cheng Fang F Lu Yinghui Y Liu Mingwei M Shi Jinsong J Liang Hongwei H Wang Yi Y Qin Jun J Zen Ke K Liu Zhihong Z

Journal of translational medicine 20230206 1

<h4>Background</h4>Diabetic nephropathy (DN) is a complex disease involving the upregulation of many inflammation-related proteins. Alternative polyadenylation (APA), a crucial post-transcriptional regulatory mechanism, has been proven to play vital roles in many inflammatory diseases. However, it is largely unknown whether and how APA exerts function in DN.<h4>Methods</h4>We performed transcriptomics and proteomics analysis of glomeruli samples isolated from 50 biopsy-proven DN patients and 25 ...[more]

PMID: 36747266

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Project description:In the budding yeast Saccharomyces cerevisiae, transcription factors (TFs) regulate the periodic expression of many genes during the cell cycle, including gene products required for progression through cell-cycle events. Experimental evidence coupled with quantitative models suggest that a network of interconnected TFs is capable of regulating periodic genes over the cell cycle. Importantly, these dynamical models were built on transcriptomics data and assumed that TF protein levels and activity are directly correlated with mRNA abundance. To ask whether TF transcripts match protein expression levels as cells progress through the cell cycle, we applied a multiplexed targeted mass spectrometry approach (parallel reaction monitoring) on synchronized populations of cells. We found that protein expression of many TFs and cell-cycle regulators closely followed their respective mRNA transcript dynamics in cycling wild-type cells. Discordant mRNA/protein expression dynamics were also observed for a subset of cell-cycle TFs and for proteins targeted for degradation by E3 ubiquitin ligase complexes such as SCF (Skp1/Cul1/F-box) and APC/C (anaphase-promoting complex/cyclosome). We further profiled mutant cells lacking B-type cyclin/CDK activity (clb1-6), where oscillations in ubiquitin ligase activity, cyclin/CDKs, and cell-cycle progression are halted. We found that a number of proteins were no longer periodically degraded in clb1-6 mutants compared to wild type, highlighting the importance of post-transcriptional regulation. Finally, the TF complexes responsible for activating G1/S transcription (SBF and MBF) were more constitutively expressed at the protein level than their periodic mRNA expression levels in both wild-type and mutant cells. This comprehensive investigation of cell-cycle regulators reveals that multiple layers of regulation (transcription, protein stability, and proteasome targeting) affect protein expression dynamics during the cell cycle.

Dataset Information

The Glomerulus Multi-Omics Analysis Provides Deeper Insights into Diabetic Nephropathy

Publications

Transcriptomics-proteomics Integration reveals alternative polyadenylation driving inflammation-related protein translation in patients with diabetic nephropathy.

Similar Datasets

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