Tissue-specific transcriptional regulation of epithelial/endothelial and mesenchymal markers during renovascular hypertension

Ferraz,Leandro  Ricardo; Moreira,Bianca  Caruso; de Queiroz,Gabriela   de Souza Rodrigues; Formigari,Regiane  de Freitas; Esquisatto,Marcelo  Augusto Marreto; Felonato,Maira; Alves,Armindo  Antonio; Thomazini,Bruna  Fontana; de Oliveira,Camila  Andréa

doi:10.3892/mmr.2019.10722

Tissue-specific transcriptional regulation of epithelial/endothelial and mesenchymal markers during renovascular hypertension

Authors:
- Leandro Ricardo Ferraz
- Bianca Caruso Moreira
- Gabriela de Souza Rodrigues de Queiroz
- Regiane de Freitas Formigari
- Marcelo Augusto Marreto Esquisatto
- Maira Felonato
- Armindo Antonio Alves
- Bruna Fontana Thomazini
- Camila Andréa de Oliveira
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Affiliations: Graduate Program in Biomedical Sciences, University Center of the Hermínio Ometto Foundation, Araras, São Paulo 13607-339, Brazil
Published online on: October 2, 2019 https://doi.org/10.3892/mmr.2019.10722
Pages: 4467-4476
Copyright: © Ferraz et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Epithelial-to-mesenchymal transition (EMT) and endothelial-to-mesenchymal transition are processes that can occur under different biological conditions, including tissue healing due to hypertension and oxidative stress. The purpose of the present study was to evaluate the differences in gene expression of epithelial/endothelial and mesenchymal markers in different tissues. A two-kidney, one-clip (2K1C) renovascular hypertension rat model was used. Hypertension was induced by the clipping of the left renal artery; the rats were randomized into sham and 2K1C groups and monitored for up to 4 weeks. The gene expressions of E-cadherin (E-cad), N-cadherin (N-cad), α-smooth muscle actin (α-SMA), collagen I (COL1A1), collagen III (COL3A1) and hepatocyte growth factor (HGF) were determined by reverse transcription-PCR. The levels of the cytokines transforming growth factor-β1, tumor necrosis factor-α, interleukin (IL)-4, IL-6 and IL-10 were evaluated using ELISAs. The levels of thiobarbituric acid reactive substances and thiol groups were measured to evaluate oxidative stress. All analyses were performed on the liver, heart and kidneys tissues of sham and model rats. The 2K1C animals exhibited a higher systolic blood pressure, as well as cardiac hypertrophy and atrophy of the left kidney. Fibrotic alterations in the heart and kidneys were observed, as was an increase in the collagen fiber areas, and higher levels of inflammatory cytokines, which are associated with the increased expression of fibroproliferative and anti-fibrotic genes. Renovascular hypertension regulated epithelial/endothelial and mesenchymal markers, including E-cad, N-cad, α-SMA and COL1A1 in the kidneys and heart. EMT in the kidneys was mediated by an increased level of inflammatory and profibrotic cytokines, as well as by oxidative stress. The data in the present study suggested that the expression of epithelial/endothelial and mesenchymal markers are differentially regulated by hypertension in the liver, heart and kidneys.

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