Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats
Background: Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play critical roles in the pathogenesis and progression of pulmonary artery hypertension (PAH). LncRNA H19, myocardial infarction-associated transcript (MIAT), miR-29a, and miR-33a have been suggested as po...
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| Format: | Article |
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KeAi Communications Co., Ltd.
2022-03-01
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| Series: | Non-coding RNA Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2468054022000051 |
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| author | Soodeh Rajabi Hamid Najafipour Mozhgan Sheikholeslami Saeideh Jafarinejad-Farsangi Ahmad Beik Majid Askaripour Zahra Miri Karam |
| author_facet | Soodeh Rajabi Hamid Najafipour Mozhgan Sheikholeslami Saeideh Jafarinejad-Farsangi Ahmad Beik Majid Askaripour Zahra Miri Karam |
| author_sort | Soodeh Rajabi |
| collection | DOAJ |
| description | Background: Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play critical roles in the pathogenesis and progression of pulmonary artery hypertension (PAH). LncRNA H19, myocardial infarction-associated transcript (MIAT), miR-29a, and miR-33a have been suggested as potential targets for treating arterial hypertension. We explored the expression pattern of non-coding RNAs H19, MIAT, miR-29a, and miR-33a in monocrotaline (MCT)-induced PAH rats. Moreover, we investigated whether perillyl alcohol (PA) and quercetin (QS), two plant derivatives with beneficial effects on PAH-induced abnormalities, act through regulating the expression of these non-coding RNAs. Methods: Male Wistar rats (n = 30) were divided into five groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered three weeks after induction of PAH. H&E staining and qRT-PCR were performed to assess arteriole wall thickness and gene expression, respectively. Results: Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) increased in MCT and MCT + Veh. groups compared to the control group (in both P < 0.001). QS and PA decreased RVSP and RVH significantly. Wall thickness and fibrosis score in the MCT group (score 3) increased compared to the control group (score 0). PA and QS ameliorated wall thickness and fibrosis to score 1 (mild). Also, the expression of miR-29a and miR-33a decreased in the PAH group (in both, P < 0.001). Treatment with PA and QS decreased the expression of H19 (P < 0.001) and MIAT (P < 0.01) and increased the expression of miR-29a (P < 0.01) and miR-33a significantly (P < 0.05 for QS and P < 0.001 for PA). Conclusions: The beneficial effects of PA and QS on PAH-induced abnormalities were exerted through returning the dysregulated expression of H19, MIAT, miR-29a, and miR-33a to normal levels in rats with MTC-induced PAH. This study emphasized the therapeutic potential of PA and QS in PAH. However, more detailed investigations are needed to clarify the underlying molecular mechanisms. |
| first_indexed | 2024-04-24T08:51:18Z |
| format | Article |
| id | doaj.art-ab8b94a8ccce4f56af234cbf5c3dc465 |
| institution | Directory Open Access Journal |
| issn | 2468-0540 |
| language | English |
| last_indexed | 2024-04-24T08:51:18Z |
| publishDate | 2022-03-01 |
| publisher | KeAi Communications Co., Ltd. |
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| series | Non-coding RNA Research |
| spelling | doaj.art-ab8b94a8ccce4f56af234cbf5c3dc4652024-04-16T12:01:24ZengKeAi Communications Co., Ltd.Non-coding RNA Research2468-05402022-03-01712733Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in ratsSoodeh Rajabi0Hamid Najafipour1Mozhgan Sheikholeslami2Saeideh Jafarinejad-Farsangi3Ahmad Beik4Majid Askaripour5Zahra Miri Karam6Student Research Committee, School of Medicine, Kerman University of Medical Sciences, Kerman, IranCardiovascular Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Science, Kerman, IranPhysiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, IranPhysiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran; Corresponding author. Physiology Research Center, Kerman University of Medical Sciences, Jehad Blvd, Ebn Sina Avenue, Kerman, 76198-13159, Iran.Endocrinology and Metabolism Research Center, Kerman University of Medical Sciences, Kerman, IranDepartment of Physiology, Bam University of Medical Sciences, Bam, IranGastroenterology and Hepatology Research Center, Kerman University of Medical Sciences, Kerman, IranBackground: Non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), play critical roles in the pathogenesis and progression of pulmonary artery hypertension (PAH). LncRNA H19, myocardial infarction-associated transcript (MIAT), miR-29a, and miR-33a have been suggested as potential targets for treating arterial hypertension. We explored the expression pattern of non-coding RNAs H19, MIAT, miR-29a, and miR-33a in monocrotaline (MCT)-induced PAH rats. Moreover, we investigated whether perillyl alcohol (PA) and quercetin (QS), two plant derivatives with beneficial effects on PAH-induced abnormalities, act through regulating the expression of these non-coding RNAs. Methods: Male Wistar rats (n = 30) were divided into five groups. MCT (60 mg/kg) was injected subcutaneously to induce PAH. PA (50 mg/kg daily) and QS (30 mg/kg daily) were administered three weeks after induction of PAH. H&E staining and qRT-PCR were performed to assess arteriole wall thickness and gene expression, respectively. Results: Right ventricular systolic pressure (RVSP) and right ventricular hypertrophy (RVH) increased in MCT and MCT + Veh. groups compared to the control group (in both P < 0.001). QS and PA decreased RVSP and RVH significantly. Wall thickness and fibrosis score in the MCT group (score 3) increased compared to the control group (score 0). PA and QS ameliorated wall thickness and fibrosis to score 1 (mild). Also, the expression of miR-29a and miR-33a decreased in the PAH group (in both, P < 0.001). Treatment with PA and QS decreased the expression of H19 (P < 0.001) and MIAT (P < 0.01) and increased the expression of miR-29a (P < 0.01) and miR-33a significantly (P < 0.05 for QS and P < 0.001 for PA). Conclusions: The beneficial effects of PA and QS on PAH-induced abnormalities were exerted through returning the dysregulated expression of H19, MIAT, miR-29a, and miR-33a to normal levels in rats with MTC-induced PAH. This study emphasized the therapeutic potential of PA and QS in PAH. However, more detailed investigations are needed to clarify the underlying molecular mechanisms.http://www.sciencedirect.com/science/article/pii/S2468054022000051Pulmonary artery hypertensionH19MIATmiR-29amiR-33aPerillyl alcohol |
| spellingShingle | Soodeh Rajabi Hamid Najafipour Mozhgan Sheikholeslami Saeideh Jafarinejad-Farsangi Ahmad Beik Majid Askaripour Zahra Miri Karam Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats Non-coding RNA Research Pulmonary artery hypertension H19 MIAT miR-29a miR-33a Perillyl alcohol |
| title | Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats |
| title_full | Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats |
| title_fullStr | Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats |
| title_full_unstemmed | Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats |
| title_short | Perillyl alcohol and quercetin modulate the expression of non-coding RNAs MIAT, H19, miR-29a, and miR-33a in pulmonary artery hypertension in rats |
| title_sort | perillyl alcohol and quercetin modulate the expression of non coding rnas miat h19 mir 29a and mir 33a in pulmonary artery hypertension in rats |
| topic | Pulmonary artery hypertension H19 MIAT miR-29a miR-33a Perillyl alcohol |
| url | http://www.sciencedirect.com/science/article/pii/S2468054022000051 |
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