TY - JOUR
T1 - Action of SNAIL1 in cardiac myofibroblasts is important for cardiac fibrosis following hypoxic injury
AU - Biswas, Hirak
AU - Longmore, Gregory D.
N1 - Funding Information:
We would like to thank Mr. Andrew Loza (Washington University in St. Louis) for assistance with immunofluorescence and birefriengence image quantification. HB was supported by an American Heart Association predoctoral fellowship (AHA Award #14PRE18680005). This work was supported, in part, by NIH grant GM080673-09 (GDL) and the Komen Foundation KG110889 (GDL). We thank the Washington University Advanced Imaging core (NIH P30DK052574), Carla Weinheimer at the Mouse Cardiovascular Phenotyping Core for surgeries, Hope Center Alafi Neuroimaging Lab for use of Nanozoomer (S10 RR0227522), and the Advanced Imaging and Tissue Analysis Core at Digestive Disease Research Core Center at Washinton University (P30DK052574).
Publisher Copyright:
© 2016 Biswas, Longmore. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2016/10
Y1 - 2016/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84991276405&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0162636
DO - 10.1371/journal.pone.0162636
M3 - Article
C2 - 27706205
AN - SCOPUS:84991276405
SN - 1932-6203
VL - 11
JO - PloS one
JF - PloS one
IS - 10
M1 - e0162636
ER -