Compatibility of Calycosin-Tanshinone IIA improves Ang II-induced renal artery endothelial cell dysfunction through lncRNA-mRNA coexpression network

Abstract

Abstract Background Long noncoding RNAs (lncRNAs) have been found to have a significant impact on the development of endothelial dysfunction. Nevertheless, the precise mechanism underlying the compatibility of Calycosin-Tanshinone IIA in mitigating the dysfunction of rat renal artery endothelial cells (RRAECs) through the coexpression network of lncRNA-mRNA remains uncertain. Methods In the present investigation, an experimental model of endothelial cell injury was established by subjecting RRAECs to Ang II (5×10− 7mol/L) for a duration of 24 h. Subsequently, this model was treated with a combination of Calycosin (3mg/L) and Tanshinone Ⅱ (3mg/L). The changes in total ATP levels and autophagy function in RRAECs were evaluated using the ATP assay and dansylcadaverine (MDC) staining, respectively. Annexin V-FITC/PI staining and transwell assay were utilized to quantify the apoptosis rate and migration function of RRAECs. Moreover, the utilization of RNA-sequencing technology facilitated the identification of differentially expressed (DE) lncRNAs and mRNAs between various groups. Subsequently, a coexpression network between DE lncRNAs and mRNAs was constructed, followed by the implementation of GO and KEGG pathway enrichment analyses to elucidate the functional implications of the DE mRNAs interacting with lncRNAs within this network. Results The compatibility of Calycosin and Tanshinone IIA had the ability to activate autophagy, decrease apoptosis rate, enhance total ATP levels, and facilitate migration of RRAECs induced by Ang II. The sequencing data demonstrated that the compatibility of Calycosin and Tanshinone IIA reversed the disordered expression of 146 DE lncRNAs and 43 DE mRNAs in Ang Ⅱ-induced RRAECs. Furthermore, a lncRNA-mRNA coexpression network consisting of 28 DE lncRNAs and 7 DE mRNAs was established. GO enrichment analyses unveiled that the DE mRNAs that interacted with lncRNAs within this network were involved in the regulation of ATPase activity, arachidonic acid metabolic process, triglyceride metabolic process. Moreover, the KEGG pathways demonstrated a significant enrichment of the MAPK signaling pathway. Conclusions The potential of Calycosin and Tanshinone IIA compatibility to mitigate the dysfunction of RRAECs induced by Ang II, possibly through the involvement of the lncRNA-mRNA coexpression network, suggested a promising avenue for intervention in delaying the progression of hypertensive renal damage.