Single-Stranded DNA-Binding Protein 1 Abrogates Cardiac Fibroblast Proliferation and Collagen Expression Induced by Angiotensin II
| Autor: | Yan-Hong Sun, Xiang Gao, Ding-Li Xu, Hai-Ping Tian, Lan He, Ya-Fang Yi |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Cardiac fibrosis Fibrillar Collagens Collagen Type I Extracellular matrix Small hairpin RNA Mitochondrial Proteins 03 medical and health sciences Mice Internal medicine medicine Animals Vasoconstrictor Agents Fibroblast Myofibroblasts Cell Proliferation Gene knockdown business.industry Angiotensin II Myocardium Heart General Medicine medicine.disease Fibrosis Collagen Type I alpha 1 Chain DNA-Binding Proteins Mice Inbred C57BL 030104 developmental biology Endocrinology medicine.anatomical_structure Collagen Type III Valsartan Heart failure cardiovascular system Tumor Suppressor Protein p53 Cardiology and Cardiovascular Medicine business Angiotensin II Type 1 Receptor Blockers Biomarkers medicine.drug |
| Zdroj: | International heart journal. 59(6) |
| ISSN: | 1349-3299 |
| Popis: | Angiotensin II (Ang II), an effective component of renin-angiotensin system, plays a pivotal role in cardiac fibrosis, which may further contribute to heart failure. Single-stranded DNA-binding protein 1 (SSBP1), a DNA damage response protein, regulates both mitochondrial function and extracellular matrix remodeling. In this study, we aim to investigate the role of SSBP1 in cardiac fibrosis that is induced by Ang II. We infused C57BL/6J mice with vehicle or Ang II and valsartan using implanted osmotic mini-pumps. Moreover, heart function was examined by echocardiography and cardiac fibrosis was analyzed via picrosirus red staining. The expression of COL1A1, COL3A1, SSBP1, p53, Nox1, and Nox4 was analyzed via qRT-PCR and/or immunoblots. The SSBP1 expression was manipulated via SSBP1 shRNA and pcDNA3.1/SSBP1 plasmids, while the p53 expression was enhanced via AdCMV-p53 infection. The exposure to Ang II increased the mouse heart weight, systolic blood pressure, interventricular septal thickness diastolic (IVSTD) and left ventricular end posterior wall dimension diastolic (LVPWD), which were counteracted by valsartan. While cardiac fibrosis was induced with Ang II treatment, it was relieved using valsartan. Furthermore, Ang II treatment caused mitochondrial dysfunction, oxidative stress, and down-regulated SSBP1 expression. The knockdown of SSBP1 increased cardiac fibroblast proliferation, collagen expression, and decreased p53 expression, which was impeded via SSBP1 overexpression. Moreover, the forced expression of p53 abated the fibroblast proliferation and collagen expression that was induced by Ang II. To summarize, SSBP1 was down-regulated by Ang II and implicated in cardiac fibroblast proliferation and collagen expression partly via the p53 protein. |
| Databáze: | OpenAIRE |
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