Chronic Obstructive Pulmonary Disease (COPD) is one of the leading cause of morbidity and death worldwide. It is characterized by chronic pulmonary inflammation and obstructed airflow from the lungs. To date, there is no effective treatments for COPD. The activation of Agrin (AGRN) - YAP pathway can promote heart regeneration. Since Agrin can only induce mild cardiomyocyte (CM) proliferation compare to ERBB2 pathway activation, it might exert pleiotropic effects, such as mitigation of innate inflammation, immune response and fibrosis. Previously, we demonstrated that several common pathologic gene regulatory programs, such as innate inflammatory and profibrotic transcriptional networks, were shared by COPD and heart failure. In this study, we show that Agrin is inversely with COPD development and progression and may exert its effects by suppressing innate inflammation and profibrotic signaling pathways. BET inhibitor JQ1, in line with our previous findings, is a promising therapeutic option in the treatment of patients with COPD. Nevertheless, wet lab experiments and clinical trials are needed before its application in clinical practice.