Role of Nrf2 and Autophagy in Acute Lung Injury

Montserrat Rojo de la Vega, Matthew Dodson, Christine Gross, Heidi M. Mansour, R. Clark Lantz, Eli Chapman, Ting Wang, Stephen Matthew Black, Joe G.N. Garcia, Donna D. Zhang

Research output: Contribution to journalReview article

25 Scopus citations

Abstract

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the clinical manifestations of severe lung damage and respiratory failure. Characterized by severe inflammation and compromised lung function, ALI/ARDS result in very high mortality of affected individuals. Currently, there are no effective treatments for ALI/ARDS, and ironically, therapies intended to aid patients (specifically mechanical ventilation, MV) may aggravate the symptoms. Key events contributing to the development of ALI/ARDS are increased oxidative and proteotoxic stresses, unresolved inflammation, and compromised alveolar-capillary barrier function. Since the airways and lung tissues are constantly exposed to gaseous oxygen and airborne toxicants, the bronchial and alveolar epithelial cells are under higher oxidative stress than other tissues. Cellular protection against oxidative stress and xenobiotics is mainly conferred by Nrf2, a transcription factor that promotes the expression of genes that regulate oxidative stress, xenobiotic metabolism and excretion, inflammation, apoptosis, autophagy, and cellular bioenergetics. Numerous studies have demonstrated the importance of Nrf2 activation in the protection against ALI/ARDS, as pharmacological activation of Nrf2 prevents the occurrence or mitigates the severity of ALI/ARDS. Another promising new therapeutic strategy in the prevention and treatment of ALI/ARDS is the activation of autophagy, a bulk protein and organelle degradation pathway. In this review, we will discuss the strategy of concerted activation of Nrf2 and autophagy as a preventive and therapeutic intervention to ameliorate ALI/ARDS.

Original languageEnglish (US)
Pages (from-to)91-101
Number of pages11
JournalCurrent Pharmacology Reports
Volume2
Issue number2
DOIs
StatePublished - Apr 1 2016

Keywords

  • Acute lung injury
  • Autophagy
  • Nrf2
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Pharmacology
  • Drug Discovery

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  • Cite this

    de la Vega, M. R., Dodson, M., Gross, C., Mansour, H. M., Lantz, R. C., Chapman, E., Wang, T., Black, S. M., Garcia, J. G. N., & Zhang, D. D. (2016). Role of Nrf2 and Autophagy in Acute Lung Injury. Current Pharmacology Reports, 2(2), 91-101. https://doi.org/10.1007/s40495-016-0053-2