Biomarker screening of rat pulmonary hypertension model by transcriptome sequencing

Abstract

To screen relative gene and pathway of rat severe pulmonary hypertension by transcriptome sequencing. Pulmonary hypertension animal model of SD rats was established by left lung resection and hypodermic injection of monocrotaline.Monocrotaline was injected subcutaneously one week after left lung resection.Eight rats at 1, 3, 5 weeks after the injection of monocrotaline respectively were named group M1, group M2 and group M3.Eight normal rats were assigned into control group (group C). The right lung tissue was used for transcriptome sequencing to screen the differentially expressed genes.KEGG pathway analysis was performed to screen the pathways with enriched differentially expressed genes. The animal model was established successfully.The pulmonary artery pressure was as follows: group C (28.6±3.0) mmHg(1 mmHg=0.133 kPa), group M1 (38.9±3.3) mmHg, group M2 (50.8±3.9) mmHg, group M3 (51.5±3.5) mmHg.The pressure elevated in group M1 compared with group C (P=0.007). The pressure in M2 and M3 elevated compared with M1(P=0.002 and P<0.001 respectively). The pressure showed no significant difference between group M3 and group M2(P=1.000). The genes possibly associated with the formation of severe pulmonary hypertension were epithelial specific receptor tyrosine kinase(Tie2) and thrombospondin-1(TSP-1). Tie2 was down-regulated (q<0.005) in the early stage of pulmonary hypertension and up-regulated (q<0.005) in the late stage of pulmonary hypertension.TSP-1 was up-regulated (q<0.005) in the early stage of pulmonary hypertension and down-regulated (q<0.005) in the late stage of pulmonary hypertension.In the stage of severe pulmonary hypertension, the differentially expressed genes were enriched mainly in the pathways of phosphatidylinostitol 3-kinase, focal adhesion kinase and extracellular matrix receptor interaction. The study provides transcriptome information of rat pulmonary hypertension model and normal rat.Possible mechanisms of pulmonary hypertension are found.These genes and pathways might be new precursor for the diagnosis and treatment of pulmonary hypertension.