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  2. LncRNA SNHG11 reprograms glutaminolysis in hepatic stellate cells via Wnt/β-catenin/GLS axis

LncRNA SNHG11 reprograms glutaminolysis in hepatic stellate cells via Wnt/β-catenin/GLS axis

  • Biochem Pharmacol. 2024 Mar:221:116044. doi: 10.1016/j.bcp.2024.116044.
Kanglei Ying 1 Yuan Zeng 1 Jun Xu 1 Xiao Wu 1 Huiya Ying 1 Weimin Cai 1 Ruoru Zhou 1 Qian Xu 1 Xiangting Zhang 2 Fujun Yu 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
  • 2 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: zhangxiangting@wmu.edu.cn.
  • 3 Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China. Electronic address: yufujun@wmu.edu.cn.
Abstract

Long non-coding RNAs (lncRNAs) have been identified as decisive regulators of liver fibrosis. Hepatic stellate cells (HSCs), major hepatic cells contributing to liver fibrosis, undergo metabolic reprogramming for transdifferentiation and activation maintenance. As a crucial part of metabolic reprogramming, glutaminolysis fuels the tricyclic acid (TCA) cycle that renders HSCs addicted to glutamine. However, how lncRNAs reprogram glutamine metabolism in HSCs is unknown. For this research, we characterized the pro-fibrogenic function of small nucleolar host gene 11 (SNHG11). Our data showed that in carbon tetrachloride (CCl4, 7 μL/g, intraperitoneally) treated C57BL/6J mice, SNHG11 expression was highly up-regulated in fibrotic livers and activated primary HSCs. SNHG11 knockdown attenuated the accumulation of fibrotic markers α-SMA and Col1A1 in liver fibrosis tissues and activated HSCs. Western blot and qRT-PCR assays demonstrated that Glutaminase (GLS), the rate-limiting Enzyme for glutaminolysis, was a downstream target of SNHG11. Furthermore, SNHG11 upregulated glutaminolysis in HSCs through the activation of the Wnt/β-catenin signaling pathway. The results highlighted that SNHG11 is a glutaminolysis-regulated lncRNA that promotes liver fibrosis. A novel insight into the metabolic mechanism that reprograms glutaminolysis in HSCs could be exploited as anti-fibrotic targets.

Keywords

Glutaminase; Hepatic stellate cell; Liver fibrosis; SNHG11; Wnt/β-catenin.

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