title: Action of SNAIL1 in Cardiac Myofibroblasts Is Important for Cardiac Fibrosis following Hypoxic Injury.
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.
authors.affiliation: Department of Cell Biology and Physiology, Washington University, St. Louis, MO, 63110, United States of America.|ICCE Institute, Washington University, St. Louis, MO, 63110, United States of America.
authors.forename: Hirak
authors.initials: H
authors.lastname: Biswas
authors.affiliation: Department of Medicine, Washington University, St. Louis, MO, 63110, United States of America.|Department of Cell Biology and Physiology, Washington University, St. Louis, MO, 63110, United States of America.|ICCE Institute, Washington University, St. Louis, MO, 63110, United States of America.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Longmore
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D015687:Cell Hypoxia; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000000981:diagnostic imaging; D051379:Mice; D018345:Mice, Knockout; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D000071250:Snail Family Transcription Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology
chemical_list: D024042:Collagen Type I; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; C000604429:Snai1 protein, mouse; D000071250:Snail Family Transcription Factors; D016212:Transforming Growth Factor beta