1. Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury
- Author
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Hirak Biswas and Gregory D. Longmore
- Subjects
0301 basic medicine ,Pathology ,Luminescence ,Platelet-derived growth factor ,Physiology ,Cardiac fibrosis ,Myocardial Infarction ,Fluorescent Antibody Technique ,Gene Expression ,lcsh:Medicine ,Aorta, Thoracic ,Biochemistry ,Extracellular matrix ,Mice ,chemistry.chemical_compound ,0302 clinical medicine ,Transforming Growth Factor beta ,Animal Cells ,Fibrosis ,Immune Physiology ,Medicine and Health Sciences ,Myocardial infarction ,Myofibroblasts ,lcsh:Science ,Cells, Cultured ,Connective Tissue Cells ,Mice, Knockout ,Platelet-Derived Growth Factor ,Innate Immune System ,Multidisciplinary ,Physics ,Electromagnetic Radiation ,Heart ,Cell Hypoxia ,Extracellular Matrix ,Connective Tissue ,030220 oncology & carcinogenesis ,Physical Sciences ,Knockout mouse ,Cytokines ,Cellular Types ,Anatomy ,Cellular Structures and Organelles ,Bioluminescence ,Myofibroblast ,Research Article ,medicine.medical_specialty ,Immunology ,Biology ,Collagen Type I ,03 medical and health sciences ,Genetics ,medicine ,Animals ,RNA, Messenger ,Myocardium ,lcsh:R ,Biology and Life Sciences ,Proteins ,Cell Biology ,Fibroblasts ,Molecular Development ,medicine.disease ,Disease Models, Animal ,Biological Tissue ,030104 developmental biology ,chemistry ,Immune System ,Heart failure ,Cardiovascular Anatomy ,lcsh:Q ,Snail Family Transcription Factors ,Collagens ,Developmental Biology - Abstract
Hypoxic injury to the heart results in cardiac fibrosis that leads to cardiac dysfunction and heart failure. SNAIL1 is a zinc finger transcription factor implicated in fibrosis following organ injury and cancer. To determine if the action of SNAIL1 contributed to cardiac fibrosis following hypoxic injury, we used an endogenous SNAIL1 bioluminescence reporter mice, and SNAIL1 knockout mouse models. Here we report that SNAIL1 expression is upregulated in the infarcted heart, especially in the myofibroblasts. Utilizing primary cardiac fibroblasts in ex vivo cultures we find that pro-fibrotic factors and collagen I increase SNAIL1 protein level. SNAIL1 is required in cardiac fibroblasts for the adoption of myofibroblast fate, collagen I expression and expression of fibrosis-related genes. Taken together this data suggests that SNAIL1 expression is induced in the cardiac fibroblasts after hypoxic injury and contributes to myofibroblast phenotype and a fibrotic scar formation. Resultant collagen deposition in the scar can maintain elevated SNAIL1 expression in the myofibroblasts and help propagate fibrosis.
- Published
- 2016