Indoxyl Sulfate Elevated Lnc-SLC15A1-1 Upregulating CXCL10/CXCL8 Expression in High-Glucose Endothelial Cells by Sponging MicroRNAs

• Published in: Toxins 2021-12, Vol.13 (12), p.873
• Main Authors: Huang, Yu-Chin, Tsai, Tzu-Chun, Chang, Chia-Hsin, Chang, Kuo-Ting, Ko, Pin-Hao, Lai, Liang-Chuan
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Atherosclerosis; Cardiovascular diseases; Cardiovascular Diseases - complications; Cardiovascular Diseases - mortality; Chemokine CXCL10 - genetics; Chemokine CXCL10 - metabolism; Chemokines; Chromosomes; CXCL10 protein; Cytokines; Diabetes; diabetes kidney disease; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Endothelial cells; Endothelial Cells - metabolism; Endothelium; Female; Gene expression; Gene Expression Regulation; Gene sequencing; Glucose; Heart diseases; human umbilical vein endothelial cells; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Humans; Immunomodulation; Indican - genetics; Indican - metabolism; indoxyl sulfate; Inflammation; Injuries; Kidney diseases; long noncoding RNAs; Male; MicroRNAs; MicroRNAs - metabolism; Middle Aged; miRNA; Mortality; Non-coding RNA; Pathogenesis; Peptide Transporter 1 - genetics; Peptide Transporter 1 - metabolism; Proteins; Renal Insufficiency, Chronic - chemically induced; Renal Insufficiency, Chronic - genetics; Renal Insufficiency, Chronic - metabolism; Sulfates; Therapeutic targets; Toxins; Toxins, Biological - toxicity; Up-Regulation
• ISSN: 2072-6651; 2072-6651
• DOI: 10.3390/toxins13120873

Cardiovascular disease (CVD) is the leading cause of mortality in diabetes mellitus (DM). Immunomodulatory dysfunction is a primary feature of DM, and the emergence of chronic kidney disease (CKD) in DM abruptly increases CVD mortality compared with DM alone. Endothelial injury and the accumulation of uremic toxins in the blood of DM/CKD patients are known mechanisms for the pathogenesis of CVD. However, the molecular factors that cause this disproportional increase in CVD in the DM/CKD population are still unknown. Since long non-protein-coding RNAs (lncRNAs) play an important role in regulating multiple cellular functions, we used human endothelial cells treated with high glucose to mimic DM and with the uremic toxin indoxyl sulfate (IS) to mimic the endothelial injury associated with CKD. Differentially expressed lncRNAs in these conditions were analyzed by RNA sequencing. We discovered that expression was significantly increased upon IS treatment in comparison with high glucose alone, and then cascaded the signal of chemokines and via sponging , , and . This novel pathway might be responsible for the endothelial inflammation implicated in augmenting CVD in DM/CKD and could be a therapeutic target with future clinical applications.