AUTHOR=Wang Lei , Zhang Wuxia , Lu Ziwen , Wang Baofu , Li Yang , Yang Jingjing , Li Peng , Zhao Mingjing 

TITLE=Functional Gene Module–Based Identification of Phillyrin as an Anticardiac Fibrosis Agent

JOURNAL=Frontiers in Pharmacology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2020.01077

DOI=10.3389/fphar.2020.01077

ISSN=1663-9812

ABSTRACT=<p>Cardiac fibrosis (CF) greatly influences the therapeutic effects of heart diseases and remains an urgent challenge in clinical therapy. Till now, only a few methods are used to find potential anti-CF drugs effectively. This study aimed to construct a gene functional module to represent the core pathological process of CF and screen antifibrotic agents capable of decreasing the expression of the gene functional module. First, three CF marker genes <italic>Postn</italic>, <italic>Ddr2</italic>, and <italic>Pdgfra</italic> were selected to identify the corresponding highest coexpressed genes in the genome-based transcriptional profiles of human hearts. Both the marker genes and the coexpressed genes formed the CF-related gene functional module. Second, the correlation of the module with the CF process was measured in a collection of gene expression profiles of heart diseases to evaluate the participation of the functional module in heart diseases. Third, the anti-CF effects of phillyrin were predicted by the enrichment analysis of the module in the phillyrin-induced transcriptional profile. Finally, the myocardial infarction animal model was used to validate the cardioprotective and anti-CF effects of phillyrin experimentally. The results showed that phillyrin was a novel antifibrotic agent in heart diseases.</p>