Danggui Buxue Decoction Ameliorates Idiopathic Pulmonary Fibrosis through MicroRNA and Messenger RNA Regulatory Network

Abstract

Objective. To develop a putative microRNA (miRNA) and messenger RNA (mRNA) regulatory network of Danggui Buxue decoction’s (DGBXD) amelioration of idiopathic pulmonary fibrosis (IPF). Methods. The Gene Expression Omnibus (GEO) database was used to identify differentially expressed miRNAs (DE-miRNAs) and differentially expressed mRNAs (DE-mRNAs). Using miRNet, the predicted target genes of identified DE-miRNAs were estimated, and then the target genes of DE-miRNAs in IPF were comprehensively examined. The Enrichr database was used to conduct functional enrichment and pathway enrichment. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was employed to obtain the target genes of DGBXD as well as active compounds. A putative miRNA-mRNA regulatory network of DGBXD acting on IPF was developed by intersecting the target genes of DGBXD with the DE-miRNA target genes in IPF. A bleomycin-induced mouse model was established and used to perform histopathology as well as real-time quantitative polymerase chain reaction (qRT-PCR) analyses of some miRNA-mRNA pairs. Results. Fourteen upmodulated DE-miRNAs and six downmodulated DE-miRNAs were screened. The downstream target genes of upmodulated and downmodulated DE-miRNAs were predicted. Subsequently, 1160 upmodulated DE-mRNAs and 1427 downmodulated DE-mRNAs were identified. Then, target genes of DE-miRNAs comprising 49 downmodulated and 53 upmodulated target genes were further screened to perform functional enrichment and pathway enrichment analyses. Subsequently, 196 target genes of DGBXD were obtained from TCMSP, with six downregulated target genes and six upregulated target genes of DGBXD acting on IPF being identified. A promising miRNA-mRNA regulatory network of DGBXD acting on IPF was developed in this study. Moreover, mir-493 together with its target gene Olr1 and mir-338 together with Hif1a were further validated by qRT-PCR. Conclusion. This study proposed detailed possible processes of miRNA-mRNA modulatory axis in IPF and constructed a prospective IPF-related miRNA-mRNA modulatory network with the aim of alleviating IPF with DGBXD.

Machine learning-based prediction of candidate gene biomarkers correlated with immune infiltration in patients with idiopathic pulmonary fibrosis

“…Recent studies have reported that IPF-related microRNAs (miRNAs) play an important role in the diagnosis and treatment of IPF (43)(44)(45). In previous studies, we have constructed a modulatory network of putative IPF-related miRNAs and messenger RNAs (mRNAs), which validates some miRNA-mRNA axes with TCM treatment of a bleomycin-induced IPF mouse model (4,46). However, a few studies have examined the With the significant advancement of science and technology, machine learning algorithms are widely used for identifying gene biomarkers and predicting disease status (51, 52).…”

“…At present, a few drugs are available for treating IPF; among which, pirfenidone and nintedanib have demonstrated evident curative effects. Traditional Chinese medicine (TCM) may play a central role in managing IPF ( 4 ). Owing to the limited understanding of the pathogenesis of IPF and the lack of early intervention strategies, IPF has become a serious life-threatening disease ( 5 ).…”