Journal Article

Transcriptomic profiling highlights cell proliferation in the progression of experimental pulmonary hypertension in rats

Yang, Lei, Bao, Changlei, Luo, Ang, Zhou, Xia, Tang, Haiyang, Chu, Ai-ai, Hao, Rongrong, Jia, Yangfan, Gu, Chenxin, Desai, Ankit A., Zhou, Lirong

2024

Overview

Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remolding and occlusion, leading to the elevated pulmonary arterial pressures, right ventricular hypertrophy, and eventual heart failure if left untreated. Understanding the molecular mechanisms underlying the development and progression of pulmonary hypertension (PH) is crucial for devising efficient therapeutic approaches for the disease. Lung homogenates were collected weekly and underwent RNA-sequencing in the monocrotaline (MCT)-induced PH rat model to explore genes associated with PH progression. Statistical analyses revealed 1038, 1244, and 3125 significantly altered genes (P < 0.05, abs (log 2 fold change) > log 2 1.5) between control and MCT-exposed rats during the first, second, and third week, respectively. Pathway enrichment analyses revealed involvement of cell cycle and innate immune system for the upregulated genes, GPCR and VEGF signaling for the downregulated genes. Furthermore, qRT-PCR validated upregulation of representative genes associated with cell cycle including Cdc25c (cell division cycle 25C), Cdc45, Top2a (topoisomerase IIα), Ccna2 (cyclin A2) and Ccnb1 (cyclin B1). Western blot and immunofluorescence analysis confirmed increases in PCNA, Ccna2, Top2a, along with other proliferation markers in the lung tissue of MCT-treated rats. In summary, RNA sequencing data highlights the significance of cell proliferation in progression of rodent PH.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 631/553 / 692/4017 / 692/53 / 692/699 / Animals / Cdc45 protein / Cell cycle / Cell division / Cell growth / Cell Proliferation / Congestive heart failure / Cyclin B1 / Disease Models, Animal / Disease Progression / G protein-coupled receptors / Gene Expression Profiling / Humanities and Social Sciences / Hypertension / Hypertension, Pulmonary - chemically induced / Hypertension, Pulmonary - genetics / Hypertension, Pulmonary - metabolism / Hypertension, Pulmonary - pathology / Hypertrophy / Immune system / Immunofluorescence / Innate immunity / Lung - metabolism / Lung - pathology / Lung diseases / Male / Molecular modelling / Monocrotaline / multidisciplinary / Pulmonary arterial hypertension / Pulmonary hypertension / Rats / Rats, Sprague-Dawley / RNA sequencing / Science / Science (multidisciplinary) / Statistical analysis / Transcriptome / Transcriptomics / Vascular endothelial growth factor