LncRNA HOTAIR regulates glucose transporter Glut1 expression and glucose uptake in macrophages during inflammation

Sci Rep. 2021 Jan 8;11(1):232. doi: 10.1038/s41598-020-80291-4.

Abstract

Inflammation plays central roles in the immune response. Inflammatory response normally requires higher energy and therefore is associated with glucose metabolism. Our recent study demonstrates that lncRNA HOTAIR plays key roles in NF-kB activation, cytokine expression, and inflammation. Here, we investigated if HOTAIR plays any role in the regulation of glucose metabolism in immune cells during inflammation. Our results demonstrate that LPS-induced inflammation induces the expression of glucose transporter isoform 1 (Glut1) which controls the glucose uptake in macrophages. LPS-induced Glut1 expression is regulated via NF-kB activation. Importantly, siRNA-mediated knockdown of HOTAIR suppressed the LPS-induced expression of Glut1 suggesting key roles of HOTAIR in LPS-induced Glut1 expression in macrophage. HOTAIR induces NF-kB activation, which in turn increases Glut1 expression in response to LPS. We also found that HOTAIR regulates glucose uptake in macrophages during LPS-induced inflammation and its knockdown decreases LPS-induced increased glucose uptake. HOTAIR also regulates other upstream regulators of glucose metabolism such as PTEN and HIF1α, suggesting its multimodal functions in glucose metabolism. Overall, our study demonstrated that lncRNA HOTAIR plays key roles in LPS-induced Glut1 expression and glucose uptake by activating NF-kB and hence HOTAIR regulates metabolic programming in immune cells potentially to meet the energy needs during the immune response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Biological Transport / genetics
  • Gene Expression Regulation / genetics*
  • Gene Knockdown Techniques
  • Glucose / metabolism*
  • Glucose Transporter Type 1 / metabolism*
  • Inflammation / metabolism
  • Macrophages / metabolism*
  • Mice
  • RNA, Long Noncoding / genetics*

Substances

  • Glucose Transporter Type 1
  • RNA, Long Noncoding
  • Glucose