OBJECTIVE: To investigate the influence of the Rho/Rho-associated kinase (ROCK) signaling pathway in rats with pulmonary arterial hypertension (PAH) under the intervention with transforming growth factor-beta 1 (TGF-β1).
MATERIALS AND METHODS: A total of 30 rats were divided into three groups using a random number table, including control group (healthy rats, n=10), model group (PAH rats, n=10), and TGF group (PAH rats injected with 5 ng/mL TGF-β1 recombinant protein, n=10). The systolic blood pressure, ventricular hypertrophy index, pathological changes in lung tissues, TGF-β1 level, protein, and messenger ribonucleic acid (mRNA) expressions of RhoA and ROCK, as well as concentrations of serum nitric oxide (NO) and endothelin-1 (ET-1) were detected via hemodynamics test, hematoxylin and eosin (HE) staining, immunohistochemical method, reverse transcription-polymerase chain reaction (RT-PCR), and enzyme-linked immunosorbent assay (ELISA).
RESULTS: The results of hemodynamics test showed that the right ventricular systolic pressure was increased markedly in model group (46.53±8.81) and TGF group (56.79±9.12) compared with that in control group (26.03±4.21) (p<0.05). The mean pulmonary systolic pressure in model group (25.89±1.92) and TGF group (29.41±1.91) was evidently higher than that in control group (15.77±2.71) (p<0.05). According to the results of heart weight measurement, model group (0.5118±0.1635) exhibited a higher ventricular hypertrophy index than control group (0.2908±0.0313) (p<0.05) but a lower ventricular hypertrophy index than TGF group (0.7231±0.1004) (p<0.05). The medial thickness of the pulmonary artery of the rats was observed through the HE staining. It was found that compared with control group, the medial thickness of the pulmonary artery was increased significantly in model group (p<0.05), while it was raised more prominently in TGF group, higher than that in model group, suggesting that TGF-β1 expression can increase the medial thickness of the pulmonary artery. It was manifested in immunohistochemical results that the protein expression of RhoA in the left lung tissues rose notably in model group compared with that in control group (p<0.05), and it was also raised remarkably in TGF group in comparison with that in model group (p<0.05), illustrating that the protein expression of TGF can activate the activity of RhoA and ROCK. The results of RT-PCR indicated that the mRNA expressions of RhoA and ROCK in the left lung tissues were elevated distinctly in model group and TGF group compared with those in control group (p<0.05), and the increases were more apparent in TGF group than those in model group (p<0.05). It was revealed in ELISA results that in comparison with control group, model group, and TGF group had markedly increased concentrations of serum NO and ET-1 (p<0.05), while the rises of serum NO and ET-1 concentrations in TGF group were the most prominent compared with those in model group (p<0.05).
CONCLUSIONS: Overexpressed TGF-β1 can activate the RhoA/ROCK signaling pathway, thus promoting the occurrence and development of PAH.Free PDF Download
To cite this article
Y. Zhang, R.-X. Yuan, D. Bao
TGF-β1 promotes pulmonary arterial hypertension in rats via activating RhoA/ROCK signaling pathway
Eur Rev Med Pharmacol Sci
Vol. 24 - N. 9