Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu2+ tripeptide complex via activation of SIRT1 in airway epithelial cells

• DOI: 10.1016/j.biopha.2023.114936
• Publication Date: 2023-05-29T11:21:07Z
• Authors: Qin Zhang; Jia Liu; Ming-ming Deng; Run Tong; Gang Hou
• Keywords: 0301 basic medicine; Ovalbumin; Lysine; Epithelial Cells; Asthma; Transforming Growth Factor beta1; Mice; Disease Models, Animal; 03 medical and health sciences; Sirtuin 1; Humans; Animals; Airway Remodeling

Fixed airflow limitation (FAO), prevalent in patients with severe or difficult-to-treat asthma, is mainly caused by airway remodeling. Airway remodeling initiated inflammation and involves subsequent pathological changes. Glycyl-l-histidyl-l-lysine (GHK) a matrikine anti-inflammatory antioxidant effects, naturally existing human tissue. At present, the GHK level plasma whether it related to of asthma remain unclear. This study was conducted determine how involved asthma. Our result showed that levels were significantly lower than those age-matched healthy controls. In patients, display moderate correlation FEF25-75%, FAO had levels. Ovalbumin-induced mice model treated PBS GHK-Cu (a form higher bioavailability) used evaluate effect exogenous supplement on administration alleviated remodeling, as reflected decreased peribronchial collagen deposition mucus secretion, suppressed epithelial-mesenchymal transition. The therapeutical TGF-β1 level. Successively, network pharmacology validation data experiments vivo vitro demonstrated increasing SIRT1 expression activating deacetylation epithelial cells, thereby alleviating Collectively, patients. Through direct binding activation SIRT1, asthmatic mice.