Altered expression of PPAR‑γ and TRPC in neonatal rats with persistent pulmonary hypertension

Du,Yanna; Fu,Jianhua; Yao,Li; Qiao,Lin; Liu,Na; Xing,Yujiao; Xue,Xindong

doi:10.3892/mmr.2017.6744

Altered expression of PPAR‑γ and TRPC in neonatal rats with persistent pulmonary hypertension

Authors:
- Yanna Du
- Jianhua Fu
- Li Yao
- Lin Qiao
- Na Liu
- Yujiao Xing
- Xindong Xue
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Affiliations: Department of Pediatrics, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, P.R. China
Published online on: June 9, 2017 https://doi.org/10.3892/mmr.2017.6744
Pages: 1117-1124
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Persistent pulmonary hypertension of the newborn (PPHN) is a life‑threatening disease that is commonly observed in the neonatal intensive care unit. PPHN is pathologically characterized by pulmonary vascular remodeling and, in particular, pulmonary artery smooth muscle cell (PASMC) proliferation. Decreased expression levels of peroxisome proliferator‑activated receptor γ (PPAR‑γ), which is a member of the nuclear receptor hormone superfamily, in combination with elevated expressions of transient receptor potential cation channel, subfamily C, member 1 (TRPC1) and TRPC6 contributes to the PASMC proliferation and excessive pulmonary vascular remodeling in adult pulmonary hypertension (PH). Whether PPAR‑γ, TRPC1 and TRPC6 affect the development of vascular remodeling in PPHN model rats remains unknown. The aim of the present study was to investigate the roles of PPAR‑γ, TRPC1 and TRP6 on the pathogenesis of PPHN in rats. The rat model of PPHN was established by exposure to hypoxic conditions and indomethacin treatment. Lung tissues, hearts and blood from PPHN model and Control rats were collected and examined. Parameters, including the percentage of medial wall thickness (WT %), the percentage of medial wall area (WA %), right ventricular hypertrophy (RVH) and the plasma concentration of B‑type natriuretic peptide (BNP) were used to estimate the development of PPHN. The expression levels of PPAR‑γ, TRPC1 and TRPC6 in lung tissues were detected by immunohistochemistry, western blotting and reverse transcription‑quantitative polymerase chain reaction. Significant increases were observed in the WT %, WA %, RVH and plasma BNP in the PPHN group compare with the Control group (P<0.01). In addition, the mRNA and protein expression levels of PPAR‑γ were markedly downregulated (P<0.05 vs. Control). In the PPHN group, the protein expression levels of TRPC1 and TRPC6 were higher compared to the control group; however, there was no difference in the mRNA expression levels (P>0.05). In conclusion, the present study successfully established a PPHN rat model, and the altered expressions of PPAR‑γ, TRPC1 and TRPC6 in the pulmonary artery located in the lungs of newborn rats with PPHN suggested that these proteins may be important mediators of PPHN.

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