Our previous study found that
tryptase activated atrial fibroblasts, increased
collagen synthesis in atrial fibroblasts through
protease activated receptor-2 (PAR2) receptors. Recent studies showed that cytoskeleton-associated
protein 4 (CKAP4) played an important role in ventricular fibroblast activation. The present study aimed to investigate the role of CKAP4 in
tryptase-induced atrial fibroblast activation, atrial
fibrosis, and molecular regulatory mechanisms. We cultured atrial fibroblasts in vitro, gave cells
tryptase stimulation, then overexpressed or silenced PAR2 and CKAP4 genes in the cells. Their effects on atrial fibroblast proliferation, migration, extracellular matrix remodeling (
Collagen I and
fibronectin) and downstream key molecules (TGF-β1, c-jun and c-fos, JNK, p38) were investigated. The results showed that the expression of CKAP4 was significantly increased by
tryptase and further increased by pcDNA3.1-PAR2, but decreased by FALLRY-NH2 and PAR2
siRNA. CKAP4 overexpression significantly increased the cell proliferation, migration and levels of
Collagen I and
fibronectin,
matrix metalloproteinase-1 (MMP-1) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in atrial fibroblasts, while CKAP4
siRNA significantly reduced them. CKAP4 overexpression significantly increased the expression of TGF-β1, c-jun and c-fos, and activated the JNK/p38 pathway, which were suppressed by CKAP4
siRNA. In conclusion, CKAP4 is involved in
tryptase-induced phenotypic conversion in atrial fibroblasts through PAR2/p38/JNK pathway, which may provide novel targets in the prevention of atrial
fibrosis.