CircHOMER1 aggravates oxidative stress, inflammation and extracellular matrix deposition in high glucose-induced human mesangial cells

Background: Circular RNAs (circRNAs) play an important regulatory role in human diseases, including diabetic nephropathy (DN). The purpose of this study was to investigate the role and mechanism of circHOMER1 action in DN.

Methods: Human mesangial cells (HMCs) were tested with high glucose (HG) to mimic DN cell models. Quantitative real-time PCR was performed to determine circHOMER1, microRNA (miR)-137 and SRY-box transcription factor 6 (SOX6) expression. SOD activity and MDA level were detected to evaluate cell oxidative stress. ELISA assay was used to analyse the levels of inflammation factors. The protein levels of extracellular matrix (ECM) deposition-related markers and SOX6 were assessed by western blot analysis. The interaction between miR-137 and circHOMER1 or SOX6 was analysed by dual-luciferase reporter assay and RNA pull-down assay.

Results: CircHOMER1 was highly expressed in HG-induced HMCs and DN patients. Downregulation of circHOMER1 suppressed oxidative stress, inflammation and ECM deposition in HMCs induced by HG. In terms of mechanism, circHOMER1 could sponge miR-137 to regulate SOX6. Function assays showed that miR-137 inhibitor or SOX6 overexpression revoked the negative regulation of circHOMER1 knockdown on HG-induced HMCs injury. In addition, miR-137 expression was negatively correlated with circHOMER1 and SOX6 expression in DN patients.

Conclusion: CircHOMER1 promoted HG-induced HMCs oxidative stress, inflammation and ECM accumulation via the miR-137/SOX6 axis, suggesting that circHOMER1 might be a target for DN treatment.