Tumor necrosis factor-related apoptosis-inducing ligand regulate the accumulation of extracelluar matrix in pulmonary artery by activating the phosphorylation of Smad2/3
| Autor: | Chan Dong Ding, Erli Yang, Xiao Bei Zhang, Qiang Sheng Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
medicine.medical_specialty
mechanism Apoptosis 02 engineering and technology Pulmonary Artery Ligands extracelluar matrix Mice Right ventricular hypertrophy In vivo medicine.artery Internal medicine 0502 economics and business pulmonary hypertension 0202 electrical engineering electronic engineering information engineering medicine QA1-939 Animals Phosphorylation Chemistry Applied Mathematics 05 social sciences tumor necrosis factor-related apoptosis-inducing ligand General Medicine medicine.disease Pulmonary hypertension Computational Mathematics medicine.anatomical_structure Endocrinology Ventricle psmad2/3 Modeling and Simulation Tumor Necrosis Factors Pulmonary artery 020201 artificial intelligence & image processing Tumor necrosis factor alpha General Agricultural and Biological Sciences 050203 business & management TP248.13-248.65 Mathematics Biotechnology |
| Zdroj: | Mathematical Biosciences and Engineering, Vol 17, Iss 2, Pp 1372-1380 (2020) |
| ISSN: | 1551-0018 |
| DOI: | 10.3934/mbe.2020069?viewType=HTML |
| Popis: | Introduction: Previous studies have found that tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was involved in the progression of pulmonary hypertension (PH), and TRAIL knocking (KO) has an inhibitory effect on PH, but its mechanism is not completely clear. Methods: The effects of TRAIL on the accumulation of extracelluar matrix (ECM), which is one of the most important processes of vascular remodeling, were observed in mice and isolated pulmonary artery smooth muscle cells (PASMCs). In vivo, mice were divided into four groups: Control group (n = 5), hypoxia-induced PH mice group (n = 8), anti-TRAIL antibody (TRAIL-Ab) treatment group (n = 8) and IgG antibody (IgG) group (n = 8). The effects of TRAIL-Ab on ECM expression in hypoxic induced PH were researched; in vivo, PASMCs were divided into three groups: Control group, hypoxia-induced group, TRAIL-Ab group. Expressions of p-Smad2/3 and p-Smad1/5/8 were compared among the three groups. Results: Hypoxia-induced PH mice had significant increases in right ventricle systolic pressure (RVSP) (P < 0.001), right ventricular hypertrophy (RVH) (P = 0.007), vascular stenosis (P < 0.001) compared with controls. Mice with anti-TRAIL antibody had lower levels in RVSP (P < 0.001), RVH (P < 0.001), vascular stenosis (P < 0.001) than PH mice. Besides, the TRAIL-Ab significantly inhibited the phosphorylation of Smad2/3 compared with hypoxia-induced group. Conclusion: TRAIL regulates the accumulation of ECM in pulmonary artery by activating pSmad2/3. |
| Databáze: | OpenAIRE |
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