Affiliation:
1. The First Affiliated Hospital of Kunming Medical University
Abstract
Abstract
Background
There are no reliable molecular targets for early diagnosis and effective treatment in the clinical management of diabetic kidney disease (DKD). To identify novel gene factors underlying the progression of DKD.
Methods
The public transcriptomic datasets of the alloxan-induced DKD model and the streptozotocin-induced DKD model were retrieved to perform an integrative bioinformatic analysis of differentially expressed genes (DEGs) shared by two experimental animal models. The dominant biological processes and pathways associated with DEGs were identified through enrichment analysis. The expression changes of the key DEGs were validated in the classic db/db DKD mouse model.
Results
The downregulated and upregulated genes in DKD models were uncovered from GSE139317 and GSE131221 microarray datasets. Enrichment analysis revealed that metabolic process, extracellular exosomes, and hydrolase activity are shared biological processes and molecular activity is altered in the DEGs. Importantly, Hmgcs2, angptl4, and Slco1a1 displayed a consistent expression pattern across the two DKD models. In the classic db/db DKD mice, Hmgcs2 and angptl4 were also found to be upregulated while Slco1a1 was downregulated in comparison to the control animals.
Conclusions
In summary, we identified the common biological processes and molecular activity being altered in two DKD experimental models, as well as the novel gene factors (Hmgcs2, Angptl4, and Slco1a1) which may be implicated in DKD. Future works are warranted to decipher the biological role of these genes in the pathogenesis of DKD.
Publisher
Research Square Platform LLC
Reference41 articles.
1. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040;Ogurtsova K;Diabetes Res Clin Pract,2017
2. Saeedi P et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition. Diabetes Res Clin Pract, 2019. 157: p. 107843.
3. Prevalence and Disease Burden of Chronic Kidney Disease;Lv JC;Adv Exp Med Biol,2019
4. New urinary biomarkers for diabetic kidney disease;Wang C;Biomark Res,2013
5. KDOQI Clinical Practice Guideline for Diabetes and CKD: 2012 Update.Am J Kidney Dis, 2012. 60(5): p.850–86.