ACPA Alleviates Bleomycin-Induced Pulmonary Fibrosis by Inhibiting TGF-β-Smad2/3 Signaling-Mediated Lung Fibroblast Activation

• DOI: 10.3389/fphar.2022.835979
• Publication Date: 2022-03-09T08:45:21Z
• Authors: Dongxin Chen; Huirong Tang; Hongchao Jiang; Lei Sun; Wenjuan Zhao; Feng Qian
• Keywords: Pharmacology; 0301 basic medicine; 03 medical and health sciences; cannabinoid type 1 receptor; transforming growth factor-beta; arachidonoylcyclopropylamide; Therapeutics. Pharmacology; RM1-950; idiopathic pulmonary fibrosis; fibroblast; 3. Good health

Pulmonary fibrosis is a group of life-threatening diseases with limited therapeutic options. The involvement cannabinoid type 1 receptors (CB1R) has been indicated in fibrotic diseases, but whether or not the activation CB1R can be benefit for treatment controversial. In this study, we investigated effects arachidonoylcyclopropylamide (ACPA), as selective agonist, on bleomycin (BLM)-induced pulmonary fibrosis. We showed that ACPA significantly improved survival rate BLM-treated mice, alleviated BLM-induced fibrosis, and inhibited expressions extracellular matrix (ECM) markers, such collagen, fibronectin, α-SMA. enhanced ECM markers transforming growth factor-beta (TGF-β)-challenged primary lung fibroblasts isolated from mouse tissues were by dose-dependent manner, fibroblast migration triggered TGF-β was dose-dependently diminished after administration. Moreover, increased mRNA levels observed both mice vivo TGF-β-challenged vitro. CB1R-specific agonist TGF-β-Smad2/3 signaling, i.e., p-Smad2 p-Smad3, decreased downstream effector proteins including slug snail, which regulate production, fibroblasts. Collectively, these findings demonstrated exhibited antifibrotic efficacy vitro models revealing novel anti-fibrosis approach to fibroblast-selective inhibition signaling targeting CB1R.