Astragaloside IV inhibits oxidized low‑density lipoprotein‑induced endothelial damage via upregulation of miR‑140‑3p

Abstract

Oxidized low-density lipoprotein (ox-LdL)-mediated endothelial cell injury has an important role in the vascular complications of type 2 diabetes. Astragaloside IV (ASV) is an active component of Radix Astragali, which has been demonstrated to exert protective effects against endothelial damage. The present study explored whether microRNAs (miRNAs) are involved in mediating the protective effects of ASV on ox-LdL-induced damage in human umbilical vein endothelial cells (HUVEcs). RNA sequencing and reverse transcription-quantitative PcR analyses revealed that ox-LdL treatment significantly downregulated miR-140-3p expression in HUVECs. miR-140-3p overexpression promoted cell proliferation and inhibited apoptosis in ox-LdL-induced HUVEcs. However, inhibition of miR-140-3p expression could reverse the effects of ASV on ox-LdL-induced HUVEcs and reactivate ASV-inhibited PI3K/Akt signaling in ox-LdL-induced HUVECs. In addition, Krüppel-like factor 4 (KLF4) was identified as a target of miR-140-3p in ox-LDL-treated HUVECs. Subsequent experiments revealed that KLF4 overexpression partially counteracted the protective effects of miR-140-3p or ASV treatment in ox-LdL-induced HUVEcs. Taken together, the current findings demonstrated that the protective effects of ASV on HUVECs were dependent on miR-140-3p upregulation and subsequent inhibition of KLF4 expression, which in turn suppressed the PI3K/Akt signaling pathway. The present results shed light to the molecular mechanism by which ASV alleviated ox-LdL-induced endothelial cell damage.

Transcriptomic Analysis Reveals the Protection of Astragaloside IV against Diabetic Nephropathy by Modulating Inflammation

“…Astragalus membranaceus (Fisch) Bge has been made as tablets for convenient application. AS-IV is a main bioactive component in Astragalus membranaceus (Fisch) Bge [37]. AS-IV has potent antidiabetes, antioxidation, anti-inflammatory, antifibrosis, and nephroprotective activities during the process of DN [17].…”

Astragaloside IV protects ATDC5 cells from lipopolysaccharide-caused damage through regulating miR-203/MyD88

“…For example, AS-IV could down-regulated miR-203a and miR-92a to protect rat cardiomyocytes from hypoxia-caused damage by down-regulation of (Gong et al 2018;Yu et al 2018). Besides, AS-IV could inhibit oxidised low-density lipoprotein-induced endothelial damage via up-regulating miR-140-3p (Qian et al 2019). These findings indicate the regulatory mechanism between AS-IV and miRNAs.…”

Circ_0068087 Silencing Ameliorates Oxidized Low-Density Lipoprotein-Induced Dysfunction in Vascular Endothelial Cells Depending on miR-186-5p-Mediated Regulation of Roundabout Guidance Receptor 1

“…There were 43 candidate miRNA targets of circ_0068087 predicted by both databases ( Supplementary Figure 2A ). Among these miRNAs, we screened out five miRNAs that were implicated in AS progression, including miR-186-5p ( 13 ), miR-140-3p ( 20 ), miR-640 ( 21 ), miR-515-5p ( 22 ), and miR-665 ( 23 ). MiR-186-5p was selected for further experiments due to it having the most significant negative regulatory relationship with circ_0068087 ( Supplementary Figure 2A ).…”

“…FIGURE 1 | Circ_0068087 is upregulated by ox-LDL in HUVECs. (A) Cell viability in HUVECs exposed to different doses of ox-LDL(10,20, 40, and 80 mg/L) for 24 h was determined by MTT assay. This experiment was performed three times with five technical repetitions each time.…”