Comparative study of the effects of baicalin and probenecid on microRNA expression profiles in porcine aortic vascular endothelial cells infected by Glaesserella parasuis.

Abstract

Background: Glaesserella parasuis elicits severe inflammatory responses and vascular damage, thus resulting in high mortality and morbidity in pigs; consequently, early diagnosis and treatment are critical to controlling economic losses. MicroRNAs (miRNAs) have been demonstrated to be involved in vascular endothelial inflammation. Baicalin is an effective Chinese medicinal herb with anti-microbial, anti-inflammatory, and anti-oxidant activity. Probenecid has activity toward multiple mammalian biological processes. Herein, we compared the effects of baicalin and probenecid on the miRNA expression profiles of porcine aortic vascular endothelial cells (PAVECs) infected with G. parasuis.

Results: We identified 277 known miRNAs and 540 novel miRNAs. Twelve miRNAs were significantly differentially expressed in PAVECs after G. parasuis infection. Both baicalin and probenecid affected the miRNA expression profiles in G. parasuis-infected PAVECs but showed different modulation patterns. Ssc-miR-27b-5p and ssc-miR-1842 were the top differentially expressed miRNAs (DEmiRNAs) in baicalin group comparing to control group. Ssc-miR-9851-3p and ssc-miR-1296-5p were the top DEmiRNAs in probenecid group. And Ssc-miR-127, ssc-miR-1842, and ssc-miR-9810-3p were the top DEmiRNAs between the baicalin group and probenecid group, as validated by qRT-PCR. The target genes of DEmiRNAs between various groups were subjected to KEGG and GO enrichment analyses. Hematopoietic cell lineage, insulin resistance, and AMPK signaling pathway were the top significantly enriched pathways associated with the target genes of DEmiRNAs in G. parasuis-infected PAVECs pretreated with baicalin; in contrast, B cell receptor, T cell receptor, and HIF-1 signaling pathways predominated in G. parasuis-infected PAVECs treated with probenecid. We additionally constructed co-expression and protein-protein interaction networks based on the differentially expressed target genes of miR-127, miR-1842, and miR-9810-3p.

Conclusion: Our findings suggested that baicalin and probenecid regulated miRNAs associated with vascular inflammation and damage, but showed different modulation patterns. This report provided the first comparison of the effects of baicalin and probenecid on G. parasuis-infected PAVECs, and might aid in the development of novel biomarkers and therapeutic targets to control G. parasuis infection.