Frontiers | Innovation and Transformation of Chronic Airway Diseases

Editorial13 December 2022

Editorial: Innovation and transformation of chronic airway diseases

Rui Zhao, Yan Chen, Yiming Ma, Chunbin Zou, 1 more and Zhihua Chen

the effect of H2S in regulating EMT and the underlying mechanisms [7] . They found that H2S inhibits cigarette smoke (CS)-or nicotine-induced ER stress and EMT in bronchial epithelial cells and alleviates CS-induced lung tissue damage and small airway fibrosis. The research suggested endogenous H2S may have an inhibitory effect on EMT related small airway fibrosis through regulating ER stress. The inositol-requiring enzyme 1 (IRE1) signal pathway and its downstream signal molecule p-Smad2/3 may be responsible for the inhibitory effect of H2S. On the other hand, Huang et al. performed untargeted metabolomics analysis of lung tissue and plasma sample, characterized the metabolic profile of lung tissue from COPD patients and found that glycerophospholipids (GPs) and amino acids metabolism disorder in male COPD patients. GPs may be related to COPD by participating in oxidative stress and inflammation [8] . Huang et al. screened and validated differential metabolites associated with male COPD and disordered metabolic pathways. They screened two two overlapping metabolites, phytosphingosine and L-tryptophan, as new promising biomarkers, could be two indicators for early screening of COPD patients. Zhang et al. investigated the effect of glycyl -L histidyl -L-lysine-Cu2+(GHK-Cu) on emphysema induced by CS [9] . GHK-Cu treatment attenuated the CS-induced emphysematous changes and partially reversed the matrix metalloprotein -9 (MMP-9)/tissue inhibitor of metalloproteinases-1 (TIMP-1) imbalance in the lung tissue. They found that GHK-Cu provides potential protection against oxidative stress and inflammation induced by CS exposure the protective effects are likely related to modulation of the NF-κB and Nrf2/Keap1 pathways. This report is the first to stress the role of GHK-Cu in an animal model of CS-induced emphysema. GHK-Cu might be a therapeutic candidate for COPD with the role of anti-inflammation and anti-oxidation. In summary, lots of studies in this research topic discuss the mechanism of chronic airway diseases and demonstrate innovative targets and biomarkers. The research topic reports the regulator roles of different biomolecules in chronic airway diseases, provides potential treatment and prevention ideas. The innovation and transformation of chronic airway diseases deserve more attention.

All authors listed have made a substantial, direct, and intellectual contribution to the work and approved it for publication.

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Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway

ORIGINAL RESEARCH

22 July 2022

Glycyl-L-histidyl-L-lysine-Cu2+ attenuates cigarette smoke-induced pulmonary emphysema and inflammation by reducing oxidative stress pathway

Qin Zhang, 2 more and Xiaoming Zhou

Background: Chronic obstructive pulmonary disease (COPD) is a common disease manifested by a persistent airflow limitation and characterized by chronic airway inflammation and lung emphysema. The cigarette smoke (CS)-induced inflammatory response and oxidative stress play essential roles in multiple cellular processes of COPD. Glycyl-L-histidyl-L-lysine (GHK) is a nontoxic and natural tripeptide involved in the process of healing and regeneration. With the combination of Cu(II), the tripeptide-copper complex glycyl-L-histidyl-L-lysine-Cu2+ (GHK-Cu) improve antioxidative and anti-inflammatory bioavailability, and they might offer potential therapeutic properties for COPD. Thus, this study aimed to explore the therapeutic effects of GHK-Cu on CS-induced emphysema. Methods: C57BL/6 mice were exposed to CS for 12 weeks to induce pulmonary emphysema. GHK-Cu was administered intraperitoneally (i.p.) at doses of 0.2, 2 and 20 µg/g/day in 100 µl of saline on alternative days from the 1st day after CS exposure. The effects of GHK-Cu on the morphology of CS-induced emphysema, the inflammatory response and oxidative stress were evaluated. We also assessed the antioxidative effect of GHK-Cu on human alveolar epithelial A549 cells. Results: GHK-Cu treatment attenuated the CS-induced emphysematous changes and partially reversed the MMP-9/TIMP-1 imbalance in the lung tissue. GHK-Cu alleviated the inflammatory response and oxidative stress by reducing the expression of TNF-α and IL-1β in the bronchoalveolar lavage fluid and the enzymatic activity of MPO and MDA in the lung homogenate while restoring the T-AOC and GSH content. Furthermore, GHK-Cu treatment reversed the CS-induced increase in NF-κB expression and increased the Nrf2 level, which is a component of the antioxidant defense system, in mice with chronic CS exposure. In CSE-exposed human alveolar epithelial A549 cells, GHK-Cu also inhibited oxidative stress by suppressing MDA levels and restoring T-AOC and GSH levels, which were modulated by upregulating Nrf2 expression. Conclusion: GHK-Cu treatment attenuated CS-induced emphysema by anti-inflammation by downregulating NF-κB and antioxidation via upregulation of the Nrf2/Keap1 pathway in lung tissues.

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