Acupuncture induces adenosine in fibroblasts through energy metabolism and promotes proliferation by activating MAPK signaling pathway via adenosine3 receptor

Acupuncture has many advantages in the treatment of certain diseases as opposed to drug therapy. Besides, adenosine has been revealed to affect cellular progression including proliferation. Therefore, this study aimed at exploring the mechanism involving acupuncture stress and adenosine in fibroblast proliferation. The fibroblasts from fascia tissues of the acupoint area (Zusanli) were stimulated by different levels of stress, different concentrations of adenosine, and agonist or antagonist of A(3) receptor (A(3)R) to investigate the effect of stress stimulation, adenosine, and adenosine-A(3)R inhibition on fibroblasts. Then, the fibroblasts were treated with stress stimulation of 200 kPa or/and mitogen-activated protein kinase (MAPK) blocker. We revealed that stress stimulation and the binding of adenosine and A(3)R promoted fibroblast proliferation in the fascial tissue, increased the expression of immune-related factors, adenosine and A(3)R, and activated the MAPK signaling pathway. MAPK signaling pathway also directly affected the expression of adenosine, A(3)R, and immune-related factors. Stress stimulation and adenosine treatment upregulated A(3)R expression, and then activated the MAPK signaling pathway, which could in turn upregulate expression of adenosine, A(3)R and immune-related factors, and promote cell proliferation. Adenosine is shown to form a positive feedback loop with the MAPK signaling pathway. Collectively, stress stimulation in vitro induces the increase of adenosine in fibroblasts through the energy metabolism and activation of the MAPK signaling pathway through A(3)R, ultimately promoting fibroblast proliferation.