biostudies-literatureYin LMShanghai Talent Development FundNational Natural Science Foundation of ChinaNational Institutes of HealthShanghai Key Research Program of Shanghai Municipal Commission of Health and Family PlanningProgram for Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learningeaam8604https://www.ebi.ac.uk/biostudies/studies/S-EPMC6310021biostudies-literatureUnknown10(427)There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than β2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces puScience translational medicineTransgelin-2 as a therapeutic target for asthmatic pulmonary resistance.PMC6310021JZ2016010award299452award357110award29945081273435award35640281774429201610R01-GM114180ZY3-CCCX-3-300581473760award350045award35710981574058award299449award299448Xu YDDeng LWu YLLi HYGe GBPang YGuan NUlloa LHuang SChen ZWang WQYang YQYin LMDuan TTLiu JYPeng LLHan XJZhu WWang YXu ZfalseTransgelin-2 as a therapeutic target for asthmatic pulmonary resistance.There is a clinical need for new bronchodilator drugs in asthma, because more than half of asthmatic patients do not receive adequate control with current available treatments. We report that inhibition of metallothionein-2 protein expression in lung tissues causes the increase of pulmonary resistance. Conversely, metallothionein-2 protein is more effective than β2-agonists in reducing pulmonary resistance in rodent asthma models, alleviating tension in tracheal spirals, and relaxing airway smooth muscle cells (ASMCs). Metallothionein-2 relaxes ASMCs via transgelin-2 (TG2) and induces dephosphorylation of myosin phosphatase target subunit 1 (MYPT1). We identify TSG12 as a nontoxic, specific TG2-agonist that relaxes ASMCs and reduces asthmatic pulmonary resistance. In vivo, TSG12 reduces pu2018-01-01T00:00:00Z2018 Feb2025-04-21T21:36:51.374Z2019-03-26T22:28:57ZS-EPMC63100212943714910.1126/scitranslmed.aam8604