20 July 2019 : Laboratory Research
Inhibitory Effects of Oxymatrine on Transdifferentiation of Neonatal Rat Cardiac Fibroblasts to Myofibroblasts Induced by Aldosterone via Keap1/Nrf2 Signaling Pathways In Vitro
Yu Yang123ABCDEF, Shiping Chen123ABCDE, Ling Tao3ABCD, Shiquan Gan23ABCD, Hong Luo23ACD, Yini Xu23ACD, Xiangchun Shen123ABCDFG*DOI: 10.12659/MSM.915542
Med Sci Monit 2019; 25:5375-5388
Abstract
BACKGROUND: Oxymatrine (OMT), a quinolizidine alkaloid derived from the traditional Chinese herb Radix Sophorae flavescentis, has widely reported pharmacological efficacy in treating cardiovascular dysfunction-related diseases. However, the underlying mechanism has been unclear. Here, we investigated the potential inhibitory effects and mechanism of OMT on transdifferentiation of cardiac fibroblast to myofibroblasts induced by aldosterone in vitro.
MATERIAL AND METHODS: The cardiac fibroblasts (CFBs) proliferation and migration capacity were evaluated by MTT assay, cell cycle assay, and scratch analysis, respectively. The protein expression of the Nrf2/Keap1 signal pathway, FN, Collagen I, Collagen III, α-SMA, CTGF, and mineralocorticoid receptor (MR) protein was detected by Western blot analysis. The mRNA expression of Nrf2 was detected by qRT-PCR. Immunofluorescence staining was used to observe the expression of α-SMA protein. Nrf2 siRNA was used to explore the role of Nrf2 in OMT-treated CFBs. GSH, SOD, and MDA levels and hydroxyproline content were measured by colorimetric assay with commercial kits. The DCFH-DA fluorescent probe was used to assess cellular ROS levels.
RESULTS: OMT and Curcumin (an Nrf2 agonist) attenuated aldosterone (ALD)-induced proliferation and migration in CFBs, as well as the fibrosis-associated protein expression levels. Moreover, OMT activated Nrf2 and promoted the nucleus translocation of Nrf2. OMT alleviated the elevated levels of α-SMA, Collagen I, Collagen III, and CTGF, which were abrogated by the Nrf2 siRNA transfection. We also found that OMT decreased oxidative stress levels.
CONCLUSIONS: Our results confirm that OMT alleviates transdifferentiation of cardiac fibroblasts to myofibroblasts induced by aldosterone via activating the Nrf2/Keap1 pathway in vitro.
Keywords: Aldosterone, Fibroblasts, NF-E2-Related Factor 2, Alkaloids, Animals, Newborn, Cell Transdifferentiation, Collagen, Fibrosis, Heart, Kelch-Like ECH-Associated Protein 1, Myocardium, myofibroblasts, Quinolizines
Editorial
01 May 2024 : Editorial
Editorial: First Regulatory Approval for Adoptive Cell Therapy with Autologous Tumor-Infiltrating Lymphocytes (TILs) – Lifileucel (Amtagvi)DOI: 10.12659/MSM.944927
Med Sci Monit 2024; 30:e944927
In Press
12 Mar 2024 : Clinical Research
Preoperative Blood Transfusion Requirements for Hemorrhoidal Severe Anemia: A Retrospective Study of 128 Pa...Med Sci Monit In Press; DOI: 10.12659/MSM.943126
12 Mar 2024 : Clinical Research
Tissue Inhibitors of Metalloproteinase 1 (TIMP-1) and 3 (TIMP-3) as New Markers of Acute Kidney Injury Afte...Med Sci Monit In Press; DOI: 10.12659/MSM.943500
12 Mar 2024 : Review article
Optimizing Behçet Uveitis Management: A Review of Personalized Immunosuppressive StrategiesMed Sci Monit In Press; DOI: 10.12659/MSM.943240
12 Mar 2024 : Clinical Research
Metabolomic Alterations in Methotrexate Treatment of Moderate-to-Severe PsoriasisMed Sci Monit In Press; DOI: 10.12659/MSM.943360
Most Viewed Current Articles
17 Jan 2024 : Review article
Vaccination Guidelines for Pregnant Women: Addressing COVID-19 and the Omicron VariantDOI :10.12659/MSM.942799
Med Sci Monit 2024; 30:e942799
14 Dec 2022 : Clinical Research
Prevalence and Variability of Allergen-Specific Immunoglobulin E in Patients with Elevated Tryptase LevelsDOI :10.12659/MSM.937990
Med Sci Monit 2022; 28:e937990
16 May 2023 : Clinical Research
Electrophysiological Testing for an Auditory Processing Disorder and Reading Performance in 54 School Stude...DOI :10.12659/MSM.940387
Med Sci Monit 2023; 29:e940387
01 Jan 2022 : Editorial
Editorial: Current Status of Oral Antiviral Drug Treatments for SARS-CoV-2 Infection in Non-Hospitalized Pa...DOI :10.12659/MSM.935952
Med Sci Monit 2022; 28:e935952