The Effects of a Transgelin-2 Agonist Administered at Different Times in a Mouse Model of Airway Hyperresponsiveness

Abstract

Airway hyperresponsiveness (AHR) is one of the most important features of asthma. Our previous study showed that inhaled transgelin-2 agonist, TSG12, effectively reduced pulmonary resistance in a mouse model of asthma in a dose-dependent manner. However, the optimal administration time of TSG12 to reduce AHR and the pharmacological effects are still unclear. In this study, the effects of TSG12 inhalation before and during AHR occurrence were examined. The results showed that the pulmonary resistance was reduced by 57% and the dynamic compliance was increased by 46% in the TSG12 Mch group (atomize TSG12 10 min before methacholine, p < 0.05 vs. model). The pulmonary resistance was reduced by 61% and the dynamic compliance was increased by 47% in the TSG12 + Mch group (atomize TSG12 and methacholine together, p < 0.05 vs. model). Quantitative real-time PCR showed that the gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 6.4-, 1.9-, and 2.8-fold, respectively, in the TSG12 Mch group. The gene expression levels of transgelin-2, myosin phosphatase target subunit-1, and myosin light chain were up-regulated by 3.2-, 1.4-, and 1.9-fold, respectively, in the TSG12 + Mch group. The results suggested that TSG12 effectively reduces pulmonary resistance when TSG12 inhalation occurred both before and during AHR occurrence. Gene expression levels of transgelin-2 and myosin light chain were significantly up-regulated when TSG12 inhalation occurred before AHR occurrence. This study may provide a basis for the administration time of TSG12 for asthma treatment in the future.

Trends of therapy in the treatment of asthma

“…For example, an inhaled transgelin-2 agonist, TSG12 is proved to reduce the airway hyperresponsiveness and effectively relieve asthma after the focused research of acupuncture. 59 The assured and favorable outcome resulted of specific novel intervention in asthma may drive the research of a series of known or unknown biomarkers quantitative abnormity that may have different levels of correlation with asthma, discover the new modulators or signal pathway of asthma, and certify the new targets associated with relieving inflammatory responses and symptom-alleviation based on regulating remodeling responses to research novel drugs.…”

Micro-simulation insights into the functional and mechanistic understanding of glycyrrhizin against asthma

“…Additionally, the lead compounds specifically binding to transgelin-2 were screened from 6,000 compounds using molecular docking techniques. Through cellular biology and a clinically relevant model of asthma, they validated that the lead compound TSG12, which relaxed the bronchial smooth muscle, had promising clinical applications as a potential anti-asthmatic drug, and they demonstrated that activation of the transgelin-2 led to bronchial smooth muscle relaxation via the “calcium sensitization” pathway ( Yuan et al, 2022 ).…”