Cuilan Hou, Lijian Xie, Tingxia Wang, Junmin Zheng, Yuqi Zhao, Qingzhu Qiu, Yi Yang, Tingting Xiao
Shanghai Children’s Hospital and Shanghai Jiao Tong University. NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology. Jin Shan Hospital and Fudan University. The Children’s Hospital and Zhejiang University School of Medicine.
China
BioMed Central Pulmonary Medicine
BMC Pulm Med 2023; 23:
DOI: 10.1186/s12890-023-02334-6
Abstract
Objectives: To investigate mRNA and long non-coding RNA (lncRNA) expression profiles in monocrotaline (MCT)- mice.
Materials and methods: Lung tissues (Control-Vehicle, MCT-Vehicle, and MCT-C75) were examined by high-throughput sequencing (HTS). Aberrantly expressed mRNAs and lncRNAs were analyzed by bioinformatics. Cell proliferation and cell cycle analysis were performed to detect the potential protective effects of C75, an inhibitor of fatty acid synthase. The signaling pathways associated with inflammatory responses were verified by real time-PCR.
Results: RNA sequencing data reveals 285 differentially expressed genes (DEGs) and 147 lncRNAs in the MCT-Vehicle group compared to the control. After five-week of C75 treatment, 514 DEGs and 84 lncRNAs are aberrant compared to the MCT-Vehicle group. Analysis of DEGs and lncRNA target genes reveals that they were enriched in pathways related to cell cycle, cell division, and vascular smooth muscle contraction that contributes to the PAH pathological process. Subsequently, the expression of eight DEGs and three lncRNAs is verified using RT-PCR. Differentially expressed lncRNAs (ENSMUSG00000110393.2, Gm38850, ENSMUSG00000100465.1, ENSMUSG00000110399.1) may associate in PAH pathogenesis as suggested by co-expression network analysis. C75 can protect against MCT-induced PAH through its anti-inflammatory and anti-proliferation.
Conclusions: These DEGs and lncRNAs can be considered as novel candidate regulators of PAH pathogenesis. We propose that C75 treatment can partially reverse PAH pathogenesis through modulating cell cycle, cell proliferation, and anti-inflammatory.
Category
Animal Models of Pulmonary Vascular Disease and Therapy
Genetic Factors Associated with Pulmonary Vascular Disease
Age Focus: No Age-Related Focus
Fresh or Filed Publication: Filed (PHiled). Greater than 1-2 years since publication
Article Access
Free PDF File or Full Text Article Available Through PubMed or DOI: Yes