Aldehyde dehydrogenase-2 acts as a potential genetic target for renal fibrosis.

Abstract

Obstructive renal injury and drug-induced nephrotoxicity are the two most common causes of renal fibrosis diseases. However, whether these two different pathogeny induced same pathological outcomes contain common genetic targets or signaling pathway, the current research has not paid great attention. GSE121190 and GSE35257 were downloaded from the Gene Expression Omnibus (GEO) database. While GSE121190 represents a differential expression profile in kidney of mice with unilateral ureteral obstruction (UUO) model, GSE35257 represents cisplatin nephrotoxicity model. By using GEO2R, 965 differential expression genes (DEGs) in GSE121190 and 930 DEGs in GSE35257 were identified. 43 co-DEGs were shared and were extracted for protein-protein interaction (PPI) analysis. Subsequently, three shared pathways including glycolysis/gluconeogenesis, fatty acid degradation and pathways in cancer were involved in two models with Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. We reconfirmed that these three pathways have relatively high scores by using Gene Set Enrichment Analysis (GSEA) software. Additionally, further bioinformatic analysis showed that Aldehyde dehydrogenase-2 (Aldh2) involved in the progression of renal fibrosis by mediating glycolysis pathway. Then real-time PCR and western blotting were performed to validate the expression of Aldh2 in kidney tissue after three different etiologies that caused renal fibrosis. Basically consistent with our bioinformatics results, our experiment showed that the expression of Aldh2 is the most significantly decreased in the UUO model, followed by ischemia-reperfusion injury (IRI) model and finally the cisplatin-induced model. Thus, Aldh2 can act as a common potential genetic target for different renal fibrosis diseases.

• Authors: Simin Tang, Teng Huang, Huan Jing, Zhenxing Huang, Hongtao Chen, Youling Fan, Jiying Zhong, Jun Zhou
• Journal: Life sciences (Life Sci) Vol. 239 Pg. 117015 (Dec 15 2019) ISSN: 1879-0631 [Electronic] Netherlands
• PMID: 31678551 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Inc. All rights reserved.

Chemical References

• ALDH2 protein, mouse
• Aldehyde Dehydrogenase, Mitochondrial
• Cisplatin

Topics

• Aldehyde Dehydrogenase, Mitochondrial (drug effects, genetics)
• Animals
• Cisplatin (toxicity)
• Computational Biology
• Databases, Genetic
• Fibrosis
• Gene Regulatory Networks (drug effects, genetics)
• Kidney Diseases (chemically induced, drug therapy, enzymology, genetics)
• Mice
• Mice, Inbred BALB C
• Protein Interaction Maps
• Ureteral Obstruction (complications, genetics, pathology)