Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy
The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardia...
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doaj-948b6a0ac11443e2aa8eb497d50234572020-11-24T23:23:54ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122016-11-01710.3389/fphar.2016.00471222361Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac HypertrophyYuan-Yuan Ding0Jing-Mei Li1Feng-Jie Guo2Ya Liu3Yang-Fei Tong4Yang-Fei Tong5Xi-Chun Pan6Xiao-Lan Lu7Xiao-Lan Lu8Wen Ye9Xiao-Hong Chen10Hai-Gang Zhang11Third Military Medical UniversityThird Military Medical UniversityNo. 309 Hospital of PLAThird Military Medical UniversityThird Military Medical UniversityChongqing Traditional Medicine HospitalThird Military Medical UniversityThird Military Medical UniversityFirst Affiliated Hospital of North Sichuan Medical CollegeThird Military Medical UniversityThird Military Medical UniversityThird Military Medical UniversityThe forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson's trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, triptolide can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes.http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00471/fullcardiac hypertrophycardiac fibrosisTriptolideCardiac InjuryForkhead box transcription factor p3 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuan-Yuan Ding Jing-Mei Li Feng-Jie Guo Ya Liu Yang-Fei Tong Yang-Fei Tong Xi-Chun Pan Xiao-Lan Lu Xiao-Lan Lu Wen Ye Xiao-Hong Chen Hai-Gang Zhang |
spellingShingle |
Yuan-Yuan Ding Jing-Mei Li Feng-Jie Guo Ya Liu Yang-Fei Tong Yang-Fei Tong Xi-Chun Pan Xiao-Lan Lu Xiao-Lan Lu Wen Ye Xiao-Hong Chen Hai-Gang Zhang Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy Frontiers in Pharmacology cardiac hypertrophy cardiac fibrosis Triptolide Cardiac Injury Forkhead box transcription factor p3 |
author_facet |
Yuan-Yuan Ding Jing-Mei Li Feng-Jie Guo Ya Liu Yang-Fei Tong Yang-Fei Tong Xi-Chun Pan Xiao-Lan Lu Xiao-Lan Lu Wen Ye Xiao-Hong Chen Hai-Gang Zhang |
author_sort |
Yuan-Yuan Ding |
title |
Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy |
title_short |
Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy |
title_full |
Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy |
title_fullStr |
Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy |
title_full_unstemmed |
Triptolide Upregulates Myocardial Forkhead Helix Transcription Factor p3 Expression and Attenuates Cardiac Hypertrophy |
title_sort |
triptolide upregulates myocardial forkhead helix transcription factor p3 expression and attenuates cardiac hypertrophy |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Pharmacology |
issn |
1663-9812 |
publishDate |
2016-11-01 |
description |
The forkhead/winged helix transcription factor (Fox) p3 can regulate the expression of various genes, and it has been reported that the transfer of Foxp3-positive T cells could ameliorate cardiac hypertrophy and fibrosis. Triptolide (TP) can elevate the expression of Foxp3, but its effects on cardiac hypertrophy remain unclear. In the present study, neonatal rat ventricular myocytes (NRVM) were isolated and stimulated with angiotensin II (1 μmol/L) to induce hypertrophic response. The expression of Foxp3 in NRVM was observed by using immunofluorescence assay. Fifty mice were randomly divided into five groups and received vehicle (control), isoproterenol (Iso, 5 mg/kg, s.c.), one of three doses of TP (10, 30, or 90μg/kg, i.p.) for 14 days, respectively. The pathological morphology changes were observed after Hematoxylin and eosin, lectin and Masson's trichrome staining. The levels of serum brain natriuretic peptide (BNP) and troponin I were determined by enzyme-linked immunosorbent assay and chemiluminescence, respectively. The mRNA and protein expressions of α- myosin heavy chain (MHC), β-MHC and Foxp3 were determined using real-time PCR and immunohistochemistry, respectively. It was shown that TP (1, 3, 10 μg/L) treatment significantly decreased cell size, mRNA and protein expression of β-MHC, and upregulated Foxp3 expression in NRVM. TP also decreased heart weight index, left ventricular weight index and, improved myocardial injury and fibrosis; and decreased the cross-scetional area of the myocardium, serum cardiac troponin and BNP. Additionally, TP markedly reduced the mRNA and protein expression of myocardial β-MHC and elevated the mRNA and protein expression of α-MHC and Foxp3 in a dose-dependent manner. In conclusion, triptolide can effectively ameliorate myocardial damage and inhibit cardiac hypertrophy, which is at least partly related to the elevation of Foxp3 expression in cardiomyocytes. |
topic |
cardiac hypertrophy cardiac fibrosis Triptolide Cardiac Injury Forkhead box transcription factor p3 |
url |
http://journal.frontiersin.org/Journal/10.3389/fphar.2016.00471/full |
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