Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu 2+ tripeptide complex via activation of SIRT1 in airway epithelial cells.

Autor: Zhang Q; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Disease, the First Hospital of China Medical University, No. 155, Nanjing Street, Heping District, 110000 Shenyang, China., Liu J; Shanghai Institute of Materia Medica, Chinese Academy of Sciences, No. 555, Zuchongzhi Road, Pudong District, Shanghai 201203, China., Deng MM; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China., Tong R; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China., Hou G; Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China; Institute of Respiratory Medicine, Chinese Academy of Medical Sciences, Beijing 100029, China; National Clinical Research Center for Respiratory Diseases, Beijing 100029, China; National Center for Respiratory Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No.2, East Yinghua Road, Chaoyang District, Beijing 100029, China. Electronic address: hougang@zryhyy.com.cn.
Jazyk: angličtina
Zdroj: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2023 Aug; Vol. 164, pp. 114936. Date of Electronic Publication: 2023 May 29.
DOI: 10.1016/j.biopha.2023.114936
Abstrakt: Fixed airflow limitation (FAO), prevalent in patients with severe or difficult-to-treat asthma, is mainly caused by airway remodeling. Airway remodeling is initiated by inflammation and involves subsequent pathological changes. Glycyl-l-histidyl-l-lysine (GHK) is a matrikine with anti-inflammatory and antioxidant effects, naturally existing in human tissue. At present, the GHK level in human plasma and whether it is related to airway remodeling of asthma remain unclear. This study was conducted to determine how GHK is involved in airway remodeling in asthma. Our result showed that the plasma GHK levels of patients with asthma were significantly lower than those of age-matched healthy controls. In asthma patients, plasma GHK levels display a moderate correlation with FEF 25-75% , and patients with FAO had significantly lower GHK levels. Ovalbumin-induced mice of asthma model treated with PBS or GHK-Cu (a form of GHK with higher bioavailability) were used to evaluate the effect of exogenous GHK supplement on airway remodeling. GHK-Cu administration alleviated airway remodeling, as reflected by decreased peribronchial collagen deposition and airway mucus secretion, and suppressed epithelial-mesenchymal transition. The therapeutical effect related to decreased TGF-β1 level. Successively, network pharmacology and the validation data of experiments in vivo and vitro demonstrated that GHK-Cu decreased TGF-β1 level by increasing SIRT1 expression and activating SIRT1 deacetylation in airway epithelial cells, thereby alleviating airway remodeling. Collectively, decreased plasma GHK levels were related to FAO in asthma patients. Through the direct binding and activation of SIRT1, exogenous GHK-Cu administration alleviated airway remodeling in asthmatic mice.
Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests.
(Copyright © 2023. Published by Elsevier Masson SAS.)
Databáze: MEDLINE
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