Long non-coding RNA HMGCR suppresses vascular remodeling in streptozotocin-induced type 1 diabetic rats via interaction with THOC5.

Abstract

Objective: This study aimed to investigate the role of long non-coding RNA (lncRNA) in vascular smooth muscle cell (VSMC) dysfunction under diabetic conditions, with a specific focus on lncHMGCR and its regulatory effects on VSMC proliferation and migration using streptozotocin-induced type 1 diabetic (T1DM) rat model and primary rat VSMCs stimulated with high glucose.

Methods: Transcriptome sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in the aortic tissues of T1DM rats. Functional enrichment analysis, including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, was conducted to elucidate potential biological roles. The expression of lncHMGCR was validated via quantitative real-time polymerase chain reaction (qRT-PCR) in the aortic tissues of T1DM rats and primary rat VSMCs pretreated with high glucose (30 mM). Functional assays were carried out to evaluate the effects of lncHMGCR overexpression and THOC5 silencing on VSMC proliferation and migration under high glucose conditions.

Results: RNA-seq analysis identified 229 differentially expressed lncRNAs (180 upregulated and 49 downregulated) in diabetic aortic tissues. GO and KEGG analyses revealed enrichment in transcriptional regulation, metal ion binding, and glycolysis-related pathways. LncHMGCR was significant downregulated in both diabetic aortic tissues and VSMCs stimulated with high glucose. Functional studies demonstrated that lncHMGCR overexpression inhibited high glucose-induced VSMC proliferation and migration by restoring THOC5 expression, whereas THOC5 knockdown exacerbated these effects.

Conclusions: This study demonstrates that lncHMGCR suppresses VSMCs dysfunction under diabetic conditions by upregulating THOC5 expression, suggesting its potential as a therapeutic target for vascular remodeling in T1DM. However, these findings are based solely on animal models and in vitro experiments, and further validation in clinical samples is required to confirm translational relevance.