KLF5/LINC00346/miR‑148a‑3p axis regulates inflammation and endothelial cell injury in atherosclerosis
| Autor: | Zikai Sun, Shenglan Huang, Ying Song, Yuan Ji, Yajing Xu, Jiyong Ge, Changle Zhou, Fangfang Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Adult
Blotting Western Kruppel-Like Transcription Factors Inflammation Nitric Oxide Umbilical vein Nitric oxide chemistry.chemical_compound Downregulation and upregulation Enos Genetics medicine Human Umbilical Vein Endothelial Cells Humans Transcription factor Cells Cultured Aged biology Chemistry Reverse Transcriptase Polymerase Chain Reaction General Medicine Middle Aged biology.organism_classification Atherosclerosis Molecular biology Endothelial stem cell Lipoproteins LDL MicroRNAs Gene Expression Regulation Cytokines RNA Long Noncoding medicine.symptom Chromatin immunoprecipitation |
| Zdroj: | International journal of molecular medicine. 48(2) |
| ISSN: | 1791-244X |
| Popis: | Atherosclerosis (AS) is the main pathological basis of cardiovascular diseases, which are related to high morbidity and mortality rates. The present study aimed to investigate the role of the Kruppel‑like factor 5 (KLF5)/LINC00346/miR‑148a‑3p loop in AS. The expression levels of KLF5 in serum and of KLF5/LINC00346/miR‑148a‑3p in human umbilical vein endothelial cells (HUVECs) were detected by RT‑qPCR analysis. The protein expression levels of KLF5, phosphorylated (p‑)endothelial nitric oxide synthase (eNOS) and eNOS in HUVECs were analyzed by western blot analysis. Changes in the levels of TNF‑α, IL‑1β, IL‑6 and nitric oxide (NO) were determined in the supernatant through the application of available commercial kits. The binding of KLF5 to the promoter region of LINC00346 was verified by chromatin immunoprecipitation (ChIP)‑PCR assay. The combinatory interaction between KLF5 and LINC00346, LINC00346 and miR‑148a‑3p, and miR‑148a‑3p and KLF5 was confirmed by luciferase reporter assay. The results revealed that KLF5 expression was increased in the serum of patients with AS and also in oxidized low‑density lipoprotein (OX‑LDL)‑stimulated HUVECs. The transcription factor KLF5 promoted the transcription of LINC00346. KLF5 interference or LINC00346 interference inhibited the expression of inflammatory factors and functional injury in OX‑LDL‑stimulated HUVECs. LINC00346 functioned as a sponge of miR‑148a‑3p. miR‑148a‑3p overexpression inhibited the expression of inflammatory factors and functional injury in OX‑LDL‑stimulated HUVECs and miR‑148a‑3p targeted KLF5 expression. On the whole, the present study demonstrates that KLF5 interference induces the downregulation of LINC00346 and also inhibits inflammation and functional injury in OX OX‑LDL‑stimulated HUVECs by upregulating miR‑148a‑3p expression. |
| Databáze: | OpenAIRE |
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