Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown. Methods In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583. Results The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-β-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression. Conclusions Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway.