2. Academic Validation
  3. Nicotinamide mononucleotide attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma

Nicotinamide mononucleotide attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma

  • Int Immunopharmacol. 2023 Dec 7:127:111328. doi: 10.1016/j.intimp.2023.111328.
Jiayuan Liang 1,  Chi Zhou 1,  Changyun Zhang 1,  Shixiu Liang 2,  Zili Zhou 1,  Zicong Zhou 2,  Cuiwen Wu 1,  Haijin Zhao 1,  Xiaojing Meng 3,  Fei Zou 3,  Changhui Yu 4,  Shaoxi Cai 5
Affiliations

Affiliations

  • 1 Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.
  • 2 Department of Allergy and Clinical Immunology, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
  • 3 Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou, Guangdong, China.
  • 4 Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: ych1029@i.smu.cn.
  • 5 Department of Respiratory and Critical Care Medicine, Chronic Airways Diseases Laboratory, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. Electronic address: hxkc@smu.edu.cn.
PMID: 38064810 DOI: 10.1016/j.intimp.2023.111328
Abstract

Nicotinamide adenine dinucleotide (NAD+) is an essential element in cellular metabolism that regulates fundamental biological processes. Growing evidence suggests that a decline in NAD+ is a common pathological factor in various diseases and aging. However, its role in airway epithelial barrier function in response to asthma remains underexplored. The current study aims to explore the efficacy of restoring cellular NAD+ concentration through supplementation with the NAD+ precursor, nicotinamide mononucleotide (NMN), in the treatment of allergic asthma and to investigate the role of SIRT3 in mediating the effects of NAD+ precursors. In this research, NMN alleviated airway inflammation and reduced mucus secretion in house dust Mite (HDM)-induced asthmatic mice. It also mitigated airway epithelial barrier disruption in HDM-induced asthma in vitro and in vivo. But inhibition of SIRT3 expression abolished the effects of NMN. Mechanistically, HDM induced SIRT3 SUMOylation and proteasomal degradation. Mutation of these two SIRT3 SUMO modification sites enhanced the stability of SIRT3. Additionally, SIRT3 was targeted by SENP1 which acted to de-conjugate SUMO. And down-regulation of SENP1 expression in HDM-induced models was reversed by NMN. Collectively, these findings suggest that NMN attenuates airway epithelial barrier dysfunction via inhibiting SIRT3 SUMOylation in asthma. Blockage of SIRT3 SUMOylation emerges as for the treatment of allergic asthma.

Keywords

Asthma; Epithelial barrier dysfunction; Nicotinamide mononucleotide; SIRT3; SUMOylation.

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