Premium
Ski inhibits Scleraxis function: Effect on collagen expression in cardiac myofibroblasts
Author(s) -
Zeglinski Matthew,
Cunnington Ryan,
Davies Jared,
Kavosh Morvarid,
Gupta Shivika,
Bathe Krista,
Rattan Sunil,
Czubryt Micheal,
Dixon Ian
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1188.10
Subject(s) - myofibroblast , cardiac fibrosis , microbiology and biotechnology , cardiac function curve , chemistry , fibrosis , fibroblast , pathology , in vitro , biology , medicine , biochemistry , heart failure
Elevated collagen deposition and increased tissue stiffness is the primary contributor to cardiac dysfunction following MI. Ski acts as a cellular brake to modulate phenoconversion of cardiac fibroblasts to myofibroblasts. Ski is associated with reduced collagen and removal of myofibroblasts from damaged heart tissues. Conversely, Scleraxis accelerates expression of collagens in cardiac myofibroblasts. We suggest that a balance exists between pro‐ and anti‐fibrotic pathways in the healthy heart and that Ski and Scleraxis are key mediators. Determine the role that Ski has on Scleraxis expression and the deposition of collagens by cardiac myofibroblasts during cardiac fibrosis. Cardiac fibroblasts were isolated from rat hearts and P1 cardiac myofibroblasts were infected at varying MOI's (10, 25, 50) with sh‐Ski or sh‐EGFP (50) control virus for 6 days. Cells were harvested for cell phenotyping and analysis of fibrillar collagens. A progressive increase in Scleraxis protein expression was noted with increasing sh‐Ski MOI from 10 to 50. This corresponded with a significant increase in mature collagen protein expression suggesting that Ski regulates Scleraxis ability to induce collagen synthesis by cardiac myofibroblasts in vitro. Ski inhibits Scleraxis function eg, to stimulate expression of collagens in cardiac myofibroblasts indicating the existence of a feedback loop between Ski and Scleraxis.