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The form and function of the rainbow trout heart can remodel in response to various stressors including changes in environmental temperature and anemia. Previous studies have hypothesized that changes in biomechanical forces experienced by the trout myocardium as result of such physiological stressors could play a role in triggering the remodeling response. However, there has been no work examining the influence of biomechanical forces on the trout myocardium or of the cellular signals that would translate such a stimuli into a biological response. In this study, we test the hypothesis that the application of biomechanical forces to trout cardiac fibroblasts activate the cell signaling pathways associated with cardiac remodeling. This was done by cyclically stretching cardiac fibroblasts to 10% equibiaxial deformation at 0.33 Hz and quantifying the activation of the p38-JNK-ERK mitogen activated protein kinase (MAPK) pathway. After 20 min, p38 MAPK phosphorylation was elevated by 4.2-fold compared to control cells ( P <0.05) and after 24 h of stretch, p38 MAPK phosphorylation remained elevated and extracellular-regulated kinase 1/2 was phosphorylated by 2.4-fold compared to control ( P <0.05). Together, these results indicate that mechanotransductive pathways are active in cardiac fibroblasts, and lead to the activation of cell signaling pathways involved in cardiac remodeling., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2020. Published by The Company of Biologists Ltd.)

The collagen content of the rainbow trout heart increases in response to cold acclimation and decreases with acclimation to warm temperatures. This ability to remodel the myocardial extracellular matrix (ECM) makes these fish useful models to study the cellular pathways involved in collagen regulation in the vertebrate heart. Remodelling of the ECM in the mammalian heart is regulated, in part, by myofibroblasts which arise from pre-existing fibroblasts in response to transforming growth factor-β1 (TGF-β1). We have previously demonstrated that treatment of cultured rainbow trout cardiac fibroblasts with human TGF-β1 causes an increase in collagen production. Here, we showed that repetitive treatment of rainbow trout cardiac fibroblasts with a physiologically relevant concentration of human recombinant TGF-β1 results in a ∼29-fold increase in phosphorylated small mothers against decapentaplegic 2 (pSmad2); a 2.9-fold increase in vinculin protein, a 1.2-fold increase in cellular size and a 3-fold increase in filamentous actin (F-actin). These are common markers of the transition of fibroblasts to myofibroblasts. Cells treated with TGF-β1 also had highly organized cytoskeletal α-smooth muscle actin, as well as increased transcript abundances of mmp-9 , timp-2 and col1a1 Furthermore, using gelatin zymography, we demonstrated that TGF-β1 treatment causes a 5.3-fold increase in gelatinase activity. Together, these results suggest that trout cardiac fibroblasts have the capacity to differentiate into myofibroblasts and that this cell type can increase extracellular collagen turnover via gelatinase activity. Cardiac myofibroblasts are, therefore, likely involved in the remodelling of the cardiac ECM in the trout heart during thermal acclimation., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)