Asiaticoside attenuates bleomycin-induced pulmonary fibrosis in A2aR−/− mice by promoting the BMP7/Smad1/5 signaling pathway

• Published in: Biochemical and biophysical research communications 2020-06, Vol.527 (3), p.662-667
• Main Authors: Zhang, Ting, Dai, Jianyi, Ye, Wenjing, Cai, Luqiong, Wei, Jinqiu, Chen, Mayun, Huang, Xiaoying, Wang, Xiaobing
• Format: Article
• Language: English
• Subjects: Adenosine 2A receptor; Animals; Asiaticoside; Bleomycin; Bone morphogenetic protein 7; Bone Morphogenetic Protein 7 - metabolism; Centella - chemistry; Gene Deletion; Male; Mice; Mice, Inbred BALB C; Pulmonary fibrosis; Pulmonary Fibrosis - chemically induced; Pulmonary Fibrosis - drug therapy; Pulmonary Fibrosis - genetics; Pulmonary Fibrosis - metabolism; Receptor, Adenosine A2A - genetics; Signal Transduction - drug effects; Smad Proteins - metabolism; Smad1/5; Triterpenes - chemistry; Triterpenes - therapeutic use
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2020.04.156

Idiopathic Pulmonary fibrosis(PF)is a chronic progressive disease, which is a lack of effective treatment,and the pathogenesis of IPF is not fully elucidated. Asiaticoside(AS) is isolated from Centella asiatica and has the effect of promoting scar healing and reducing scar formation. However,its possible role in idiopathic pulmonary fibrosis remains unclear. Adenosine A2A receptor (A2AR) is reported a protective factor in pulmonary fibrosis, and the bone morphogenetic protein 7 (BMP7) signaling pathway plays a crucial role in fibrosis in multiple organs. But the impact of A2AR on the BMP7 pathway has not yet been reported. Therefore, we hypothesized AS may promote the expression of A2AR, and then influence the BMP7/Smad1/5 pathway to alleviate pulmonary fibrosis. A2AR−/− mice and wild-type (WT) mice were administered bleomycin (BLM) by intratracheal injection. AS (50 mg/kg/d) was given daily for 28 days. AS reduced collagen deposition in lung tissue, interstitial lung inflammation. Furthermore, AS promoted A2AR expression and BMP7 pathway. Collectively, AS may attenuate BLM-induced pulmonary fibrosis by upregulating the BMP7 signaling pathway through A2AR. •Asiaticoside could relieve BLM-induced pulmonary fibrosis in wild-type（WT） mice and A2AR−/−（KO）mice.•Asiaticoside could promote the expression of A2aR in the lung tissue of WT mice, but has no effect on A2AR−/− mice.•AS could promote the BMP7/Smad1/5 pathway, and compared to KO mice, AS has an obvious effect of this pathway in WT mice.•Compared to A2AR−/− mice, the expression of BMP7 and p-Smad1/5 is obvious in WT mice.