Relief of ovalbumin-induced airway remodeling by the glycyl-l-histidyl-l-lysine-Cu<sup>2+</sup> tripeptide complex via activation of SIRT1 in airway epithelial cells.
Zhang. Qin Q; Liu. Jia J; Deng. Ming-Ming MM; Tong. Run R; Hou. Gang G
Key Findings
- Asthma patients show significantly reduced plasma GHK levels, especially those with fixed airflow limitation.
- Administering GHK‑Cu to asthmatic mice lessened airway remodeling, collagen buildup, and mucus production.
- GHK‑Cu works by boosting SIRT1 activity in airway cells, which suppresses TGF‑β1‑driven tissue changes.
Practical Outcomes
- The study suggests that boosting GHK (especially the copper‑bound form) could help protect lung tissue by activating SIRT1, a pathway many biohackers target for anti‑aging. However, the evidence is currently limited to animal models, so any supplementation should be experimental and done with caution. No human dosage or safety data are provided, so enthusiasts should wait for clinical trials before adopting it as a routine asthma or lung‑health protocol.
Summary
People with asthma have lower levels of a natural peptide called GHK in their blood, and the amount of GHK is linked to how well their lungs work. In mice, giving a more bioavailable form of this peptide (GHK‑Cu) reduced the thickening and scarring of airway tissue that normally makes breathing harder. The benefit seems to come from the peptide turning on a protein called SIRT1, which then lowers a fibrosis‑promoting signal (TGF‑β1).
Abstract
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<sub>25-75%</sub>, 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.
Study Information
pubmed
2023
2023-05-29T00:00:00.000Z
10.1016/j.biopha.2023.114936
6
49