Numerous studies have revealed that hyperglycemia is a pivotal driver of diabetic vascular complications. However, the mechanisms of hyperglycemia-induced endothelial dysfunction in diabetes remain incompletely understood. This study aims to expound on the underlying mechanism of the endothelial dysfunction induced by hyperglycemia from the perspective of long non-coding RNAs (lncRNA). In this study, a downregulation of SNHG15 was observed in the ischemic hind limb of diabetic mice and high glucose (HG)-treated HUVECs. Functionally, the overexpression of SNHG15 promoted cell proliferation, migration, and tube formation, and suppressed cell apoptosis in HG-treated HUVECs. Mechanistically, SNHG15 reduced thioredoxin-interacting protein (TXNIP) expression by enhancing ITCH-mediated ubiquitination of TXNIP. TXNIP overexpression abrogated the protective effect of lncRNA SNHG15 overexpression on HG-induced endothelial dysfunction. The following experiment further confirmed that SNHG15 overexpression promoted angiogenesis of the ischemic hind limb in diabetic mice. In conclusion, SNHG15 is a novel protector for hyperglycemia-induced endothelial dysfunction via decreasing TXNIP expression.
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The datasets generated and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.
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This work was supported by the Major Science and Technology Project in Medical and Health of Zhejiang Province (co-constructed Project by Province and the Ministry, 2020380400, WKJ-ZJ-2003) and the Key Program of Natural Science Foundation of Zhejiang Province (LZ21H020001).
Conflict of interest
The authors declare no competing interests.
All animal experiments were approved by the Ethics Committee of the The First Affiliated Hospital, School of Medicine, Zhejiang University.
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Zhu, Qq., Lai, Mc., Chen, Tc. et al. LncRNA SNHG15 relieves hyperglycemia-induced endothelial dysfunction via increased ubiquitination of thioredoxin-interacting protein. Lab Invest (2021). https://doi.org/10.1038/s41374-021-00614-5