Cathepsin S-mediated fibroblast trans-differentiation contributes to left ventricular remodelling after myocardial infarction

Abstract

Along with its established activities in ECM degradation, CatS plays novel roles in TGF-β1 signalling, myofibroblast trans-differentiation, and ECM protein synthesis, thereby regulating scar formation in the infarcted myocardium and preserving LV function after experimental MI.

Regulation of TGF-β1-driven Differentiation of Human Lung Fibroblasts

“…1a). Conversely, we did not detect Cat S (proform and mature enzyme) as reported for cardiac fibroblasts (21). Secreted Cats B, L, and K, but not Cat S, were mostly found as zymogens in culture media, whereas their mature forms were weakly stained (Fig.…”

“…Also, expression of Cat B is increased during differentiation of stellate cells, and data support that Cat B participates in liver fibrogenesis (20). Alternatively, the inhibition of Cat S may impair the TGF-␤1-dependent differentiation of cardiac fibroblasts in a model of myocardial infarction (21). Some apparently conflicting results were reported for lung fibrosis.…”

“…Expression of Cat B is enhanced during hepatic stellate cell activation and parallels the increase of TGF-␤1 and ␣-SMA, supporting that Cat B may drive hepatic stellate cell transdifferentiation and hence participates in liver fibrogenesis (20). Alternatively, it has been suggested that the inhibition of Cat S may disturb TGF-␤1 signaling and impair the differentiation of fibroblasts in a murine model of myocardial infarction (21).…”

Cathepsin S: therapeutic, diagnostic, and prognostic potential

“…In diabetes, cathepsin S serum levels have been shown to be increased when compared to normal healthy patient serum (Chen et al, 2013b;Jobs et al, 2013). Interestingly a correlation between diabetes and endogenous cathepsin inhibitor cystatin C was also observed (Liu et al, 2006).…”

Systems biology—opportunities and challenges: the application of proteomics to study the cardiovascular extracellular matrix

“…For example, in a recent study we demonstrated that genetic deletion of biglycan was accompanied by an unexpected rise of aggrecan in murine aortas 44 Table 1Role of ECM and ECM-associated proteins in cardiac diseaseProteinClinical contextMain findingsAdiponectinCardiac remodelling (m)Induces cell migration, MMP activation, and collagen remodelling via APPL1-AMPK signalling 6 ADAMTS9Developmental defects (m)Haploinsufficiency leads to reduced versican cleavage, associated with cardiac anomalies 7 BiglycanMI (m)Required for adaptive remodelling 8 Cathepsin-KAF (h, rb)Increased levels and activity accompanied atrial changes linked to the AngII/ATR1R signalling pathway 9 Cathepsin-SMI (m)Mediates fibroblast transdifferentiation during remodelling 10 Collagen IDilated cardiomyopathy (m)Point mutation induces cardiomyopathy 11 Collagen VIMI (m)Absence improves cardiac function, structure, and remodelling 12 Collagen XIVDevelopmental defects (m)Important for growth and structural integrity of the myocardium 13 Collagen XVHypertension (m)Necessary for remodelling. Deficiency predisposes to cardiomyopathy 14 Connective tissue growth factorPressure overload (m)Inhibition attenuates left ventricular remodelling and dysfunction 15 DecorinLeft ventricular assist device implantation (h)Ameliorates adverse remodelling by mediating TGF-beta inhibition 16 MI (m)Absence leads to abnormal scar tissue formation 17 FibronectinMI (m, h)Essential for progenitor cell response during cardiac repair 18 …”