Inhibitor of DNA Binding 1 Is Induced during Kidney Ischemia-Reperfusion and Is Critical for the Induction of Hypoxia-Inducible Factor-1α

• Published in: BioMed research international Vol. 2016; no. 2016; pp. 1 - 10
• Main Authors: Feng, Xiao-Bei, Shi, Hao, Zhang, Wen, Xu, Jing, Xu, Yao-Wen, Shen, Ping-Yan, Xie, Yin-Yin, Zhao, Qian, Gao, Yao-Hui, Zou, Yan-Fang, Wen, Dan, Chen, Yong-Xi
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2016
• Subjects: Acute Kidney Injury - genetics; Acute Kidney Injury - pathology; Animals; Cell Hypoxia - genetics; Disease Models, Animal; Epithelial Cells - metabolism; Epithelial Cells - pathology; Gene Expression; Gene Silencing; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - antagonists & inhibitors; Hypoxia-Inducible Factor 1, alpha Subunit - biosynthesis; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Inhibitor of Differentiation Protein 1 - biosynthesis; Inhibitor of Differentiation Protein 1 - genetics; Kidney Tubules, Distal - metabolism; Kidney Tubules, Distal - pathology; Rats; Reperfusion Injury - genetics; Reperfusion Injury - pathology; RNA, Messenger - biosynthesis
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2016/4634386

In this study, rat models of acute kidney injury (AKI) induced by renal ischemia-reperfusion (I/R) and HK-2 cell models of hypoxia-reoxygenation (H/R) were established to investigate the expression of inhibitor of DNA binding 1 (ID1) in AKI, and the regulation relationship between ID1 and hypoxia-inducible factor 1 alpha (HIF-1α). Through western blot, quantitative real-time PCR, immunohistochemistry, and other experiment methods, the induction of ID1 after renal I/R in vivo was observed, which was expressed mainly in renal tubular epithelial cells (TECs). ID1 expression was upregulated in in vitro H/R models at both the protein and mRNA levels. Via RNAi, it was found that ID1 induction was inhibited with silencing of HIF-1α. Moreover, the suppression of ID1 mRNA expression could lead to decreased expression and transcription of HIF-1α during hypoxia and reoxygenation. In addition, it was demonstrated that both ID1 and HIF-1α can regulate the transcription of twist. This study demonstrated that ID1 is induced in renal TECs during I/R and can regulate the transcription and expression of HIF-1α.