Scleraxis is a mechanoresponsive regulator of the cardiac myofibroblast phenotype

Simple item page
dc.contributor.authorRoche, Patricia
dc.contributor.examiningcommitteeDixon, Ian (Physiology and Pathophysiology) Zahradka, Peter (Physiology and Pathophysiology) Wigle, Jeffrey (Biochemistry and Medical Genetics)en_US
dc.contributor.supervisorCzubryt, Michael (Physiology and Pathophysiology)en_US
dc.date.accessioned2015-04-07T18:43:29Z
dc.date.available2015-04-07T18:43:29Z
dc.date.issued2015-04-07
dc.degree.disciplinePhysiology and Pathophysiologyen_US
dc.degree.levelMaster of Science (M.Sc.)en_US
dc.description.abstractCardiac fibrosis is the excess deposition of myocardial extracellular matrix components, which increases tissue stiffness and heterogeneity, causing impaired diastolic/systolic function and arrhythmias, and eventually leading to heart failure and death. There are no available treatments for cardiac fibrosis. Myofibroblasts mediate fibrosis, and are characterized by hypersynthesis of collagens, decreased migration, and increased α-smooth muscle actin, which is incorporated into stress fibers, imparting contractility. Scleraxis is a transcriptional regulator of collagen-rich tissues, increased in response to the same stimuli that drive the myofibroblast phenotype, such as cyclic stretch. We show that Scleraxis mediates the conversion of cardiac fibroblasts to myofibroblasts, by increasing myofibroblast marker expression and contraction, and decreasing migration. Additionally, a proximal 1500 bp human SCLERAXIS promoter is activated by stretch and is responsive to transforming growth factor-β1. Thus, Scleraxis is a specific mechanoresponsive regulator of the myofibroblast, representing a novel target for the treatment of cardiac fibrosis.en_US
dc.description.noteMay 2015en_US
dc.identifier.urihttp://hdl.handle.net/1993/30354
dc.language.isoengen_US
dc.rightsopen accessen_US
dc.subjectFibroblasten_US
dc.subjectMyofibroblasten_US
dc.subjectCardiac fibrosisen_US
dc.subjectScleraxisen_US
dc.titleScleraxis is a mechanoresponsive regulator of the cardiac myofibroblast phenotypeen_US
dc.typemaster thesisen_US
Files
Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
roche_patricia.pdf
Size:
2.58 MB
Format:
Adobe Portable Document Format
Description:
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.25 KB
Format:
Item-specific license agreed to upon submission
Description:
Download
Collections
FGS - Electronic Theses and Practica