Role of pterostilbene in the regulation of notch signaling pathway of pulmonary fibrosis; comprehensive bioinformatics analysis model and in vivo study

Abstract

Abstract BACKGROUND Pulmonary fibrosis (PF) is a chronic progressive interstitial lung disease caused by a variety of factors. To investigate the role of the Notch pathway in idiopathic pulmonary fibrosis (IPF) patients and of pterostilbene in Notch pathway regulation employing systematic bioinformatic model followed by the analysis of pterostilbene role in alleviating the bleomycin (BLM)-induced pulmonary fibrosis (PF) in rats. METHODS Bioinformatics analysis was performed to screen and analyze the differentially expressed genes (DEGs) related to PF, and further narrowed to those associated with the Notch signaling pathway and explore the mechanism of Notch and related genes on the pathological process of PF involved in the differential gene expression in the human lung and pterostilbene interaction with relevant proteins. For further confirmation, we induced PF in mice using BLM. Moreover, the effect of pterostilbene on the proliferation phenotype of BLM-induced PF was probed employing qRT-PCR analysis. RESULTS Following a systematic bioinformatics analysis model followed by experimental validations, we observed that Notch was upregulated in IPF patients and induced mice. Moreover, the results revealed that pterostilbene had activated SOD1 in lung fibroblasts, which led to the inhibition of the Notch signaling pathway via the reduction of the ROS levels. CONCLUSION We demonstrated that Notch overexpression is a key factor in inducing PF. Interestingly, our observations showed that pterostilbene’s primary function on PF is to regulate the Notch signaling pathway via activation of SOD1, reducing the ROS levels.