2. Academic Validation
  3. An oxygen-adaptive interaction between SNHG12 and occludin maintains blood-brain barrier integrity

An oxygen-adaptive interaction between SNHG12 and occludin maintains blood-brain barrier integrity

  • Cell Rep. 2022 Apr 12;39(2):110656. doi: 10.1016/j.celrep.2022.110656.
Yuan Li 1,  Jia-Yi Wei 1,  Hui Liu 1,  Kang-Ji Wang 1,  Sheng-Nan Jin 1,  Zheng-Kang Su 1,  Hui-Jie Wang 1,  Jun-Xiu Shi 1,  Bo Li 1,  De-Shu Shang 1,  Wen-Gang Fang 1,  Xiao-Xue Qin 1,  Wei-Dong Zhao 2,  Yu-Hua Chen 3
Affiliations

Affiliations

  • 1 Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China; Department of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China.
  • 2 Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China; Department of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China. Electronic address: wdzhao@cmu.edu.cn.
  • 3 Department of Developmental Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China; Department of Developmental Cell Biology, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, 77 Puhe Road, Shenbei New District, 110122 Shenyang, China. Electronic address: yhchen@cmu.edu.cn.
PMID: 35417709 DOI: 10.1016/j.celrep.2022.110656
Abstract

Tight junctions (TJs) of brain microvascular endothelial cells (BMECs) play a pivotal role in maintaining the blood-brain barrier (BBB) integrity; however, precise regulation of TJs stability in response to physiological and pathological stimuli remains elusive. Here, using RNA immunoprecipitation with next-generation Sequencing (RIP-seq) and functional characterization, we identify SNHG12, a long non-coding RNA (lncRNA), as being critical for maintaining the BBB integrity by directly interacting with TJ protein occludin. The interaction between SNHG12 and occludin is oxygen adaptive and could block Itch (an E3 ubiquitin Ligase)-mediated ubiquitination and degradation of occludin in human BMECs. Genetic ablation of endothelial Snhg12 in mice results in occludin reduction and BBB leakage and significantly aggravates hypoxia-induced BBB disruption. The detrimental effects of hypoxia on BBB could be alleviated by exogenous SNHG12 overexpression in brain endothelium. Together, we identify a direct TJ modulator lncRNA SNHG12 that is critical for the BBB integrity maintenance and oxygen adaption.

Keywords

CP: Cell biology; blood-brain barrier; endothelium; hypoxia; tight junction.

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