Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Mar 17;24(1):127.
doi: 10.1186/s12864-023-09222-7.

Proteomics and transcriptomics profiling reveals distinct aspects of kidney stone related genes in calculi rats

Wang Zhu #  1 , Deng Qiong #  1 , Gu Yanli  2 , Li Min  3 , Zhang Ying  1 , Hu Qiyi  1 , Zhang Shenping  1 , Wang Xisheng  4 , Liang Hui  5
Affiliations

Proteomics and transcriptomics profiling reveals distinct aspects of kidney stone related genes in calculi rats

Wang Zhu et al. BMC Genomics. .

Abstract

Backgrounds: Kidney stone also known as urolithiasis or nephrolithiasis, is one of the oldest diseases known to medicine, however, the gene expression changes and related kidney injury remains unclear.

Methods: A calculi rat model was developed via ethylene glycol- and ammonium chloride-induction. Integrated proteomic and transcriptomic analysis was performed to characterize the distinct gene expression profiles in the kidney of calculi rat. Differential expressed genes (DEGs) were sub-clustered into distinct groups according to the consistency of transcriptome and proteome. Gene Ontology and KEGG pathway enrichment was performed to analyze the functions of each sub-group of DEGs. Immunohistochemistry was performed to validated the expression of identified proteins.

Results: Five thousand eight hundred ninety-seven genes were quantified at both transcriptome and proteome levels, and six distinct gene clusters were identified, of which 14 genes were consistently dysregulated. Functional enrichment analysis showed that the calculi rat kidney was increased expression of injured & apoptotic markers and immune-molecules, and decreased expression of solute carriers & transporters and many metabolic related factors.

Conclusions: The present proteotranscriptomic study provided a data resource and new insights for better understanding of the pathogenesis of nephrolithiasis, will hopefully facilitate the future development of new strategies for the recurrence prevention and treatment in patients with kidney stone disease.

Keywords: Calcium oxalate; Kidney stone; Proteomics; Transcriptomics; Urolithiasis.

PubMed Disclaimer

Conflict of interest statement

The authors declare seriously that external funding sources and interest conflicts did not exist in the study.

Figures

Fig. 1
Fig. 1
Study design and validation of the calculi rat model. A Study design and workflow of rat kidney sample processing for proteomics and transcriptomics analysis. B Histochemical validation of the calcium crystals in the calculi rat model via HE staining and von Kossa’s staining. The arrows indicate the calculi oxalate crystals. Original magnification, × 40
Fig. 2
Fig. 2
Sample qualification. A FPKM box diagram. The abscissa in the figure represents different samples. The ordinate represents the logarithm of the sample expression FPKM. The figure measures the expression level of each sample from the perspective of the overall dispersion of the expression amount. B The Pearson correlation of all samples. C Overview of protein identification. D Principal component analysis (PCA) to evaluate the repeatability of protein quantification
Fig. 3
Fig. 3
Overview of transcriptomic analysis. A Volcano plot of differential expressed genes in the kidney of calculi rat. B GO terms enrichment of the DEGs. C KEGG enrichment analysis of differential gene. D Statistics of pathway enrichment
Fig. 4
Fig. 4
Proteomic profiling of the kidney in calculi rats. A Volcano plot of differential expressed proteins. B Statistical chart of differential expressed proteins. C GO function classification. D Subcellular annotation of up-regulated proteins. E Subcellular annotation of down-regulated proteins
Fig. 5
Fig. 5
Functional enrichment analysis of differentially expressed proteins. A Biological process. B Cellular component. C Molecular function. D KEGG pathway. E Clustering analysis. Up: the differential expressed proteins were divided into four groups (Q1 to Q4) according to their expression level. Down: heatmap of the biological process terms of each subgroup. The color bar indicates the enrichment degree
Fig. 6
Fig. 6
Distinct gene expression profiles identification by integrated proteomic and transcriptomic analysis. A Wayne diagram for quantitative comparison of transcriptome and proteome. B Scatter plot of transcript and its corresponding protein expression. C Wayne diagram analysis of differentially expressed proteins and transcripts. D Cellular component of proteins in up-up group. E Biological process of proteins in up-up group. F Molecular function of proteins in up-up group. G KEGG analysis of proteins in up-up group. H Molecular function of proteins in down-down group. I KEGG analysis of proteins in down-down group
Fig. 7
Fig. 7
Verification of the DEPs by IHC analysis. Original magnification, × 40. The histogram profile corresponds to the pixel intensity value vs. corresponding number counts of a pixel intensity
Fig. 8
Fig. 8
An overview of possible biological changes that might contribute to crystal formation in the kidney of calculi rats
See this image and copyright information in PMC

References

    1. Li CC, Chien TM, Wu WJ, Huang CN, Chou YH. Uric acid stones increase the risk of chronic kidney disease. Urolithiasis. 2018;46(6):543–547. doi: 10.1007/s00240-018-1050-1. - DOI - PubMed
    1. Taylor EN, Feskanich D, Paik JM, Curhan GC. Nephrolithiasis and Risk of Incident Bone Fracture. J Urol. 2016;195(5):1482–1486. doi: 10.1016/j.juro.2015.12.069. - DOI - PMC - PubMed
    1. Shadman A, Bastani B. Kidney Calculi: Pathophysiology and as a Systemic Disorder. Iran J Kidney Dis. 2017;11(3):180–191. - PubMed
    1. Bishop K, Momah T, Ricks J. Nephrolithiasis. Prim Care. 2020;47(4):661–671. doi: 10.1016/j.pop.2020.08.005. - DOI - PubMed
    1. Sakhaee K, Maalouf NM, Kumar R, Pasch A, Moe OW. Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney Int. 2011;79(4):393–403. doi: 10.1038/ki.2010.473. - DOI - PMC - PubMed

LinkOut - more resources