Drug Design, Development and Therapy (Jul 2022)
Icariin and Competing Endogenous RNA Network: A Potential Protective Strategy Against Contrast-Induced Acute Kidney Injury
Abstract
Yan Lin,1,2,* Gaofeng Zhu,3,* Xiaoyong Li,4,* Huaxiao Yu,5 Yuhang Luo,5 Jiaqiong Lin,6 Renyuan Li,7 Zena Huang2 1Department of Nephrology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China; 3Department of General Medicine, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, People’s Republic of China; 4Department of General Surgery, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 5The Third Clinical School, Guangzhou Medical University, Guangzhou, People’s Republic of China; 6Affiliated Dongguan Maternal and Child Healthcare Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 7Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zena Huang, Yunkang School of Medicine and Health, Nanfang College, Guangzhou, People’s Republic of China, Tel +86-13570466614, Email [email protected] Renyuan Li, Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China, Tel +86-18926146852, Email [email protected]: Icariin presents protective effect in several kidney diseases. However, the role of icariin in contrast-induced acute kidney injury (CIAKI) is still unclear. This study aimed to investigate the effect of icariin in CIAKI, as well as exploring the underlying mechanism from the aspect of interaction between protein-coding genes and non-coding RNAs.Methods: The effect of icariin was evaluated in both in vivo and in vitro CIAKI models. Rat kidneys were collected for genome-wide sequencing. The differentially expressed genes (DEGs) were screened and visualized by R software. The function annotation of DEGs was analyzed by Metascape. By Cytoscape software, the competing endogenous RNA (ceRNA) network was constructed, and hub genes were selected. Expressions of hub genes were validated by PCR. Association of hub genes in the ceRNA network and renal function was also examined.Results: Icariin protected against CIAKI in both in vivo and in vitro models. Based on DEGs in icariin pretreated CIAKI rats, lncRNA- and circRNA-associated ceRNA networks were constructed, respectively. Function annotation showed the ceRNA networks were enriched in ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling. Further, two circRNAs, six lncRNAs, four miRNAs and nine mRNAs were selected as hub genes of the ceRNA network. Among them, eight mRNAs (Acot1, Cbwd1, Ly6i, Map3k14, Mettl2b, Nyap1, Set and Utp20) were negatively correlated with renal function, while one mRNA (Tmem44) was positively correlated with renal function.Conclusion: Icariin presented a protective effect against CIAKI. The ceRNA network, involving Acot1, Cbwd1, Ly6i, Map3k14, Mettl2, Nyap1, Set, Tmem44 and Utp20, might partially contribute to the underlying mechanism of icariin protection by regulation of ERK1 and ERK2 cascade, MAPK signaling and NF-κB signaling.Keywords: icariin, contrast medium, acute kidney injury, competing endogenous RNA, non-coding RNA
