Fig. 2

Major signaling pathways involved in cardiac fibrosis. Mechanosensitive pathways play a pivotal role in activating fibroblasts during various cardiac pathological conditions. Integrins, mechanosensitive ion channels, and activation of G-protein coupled receptors all initiate signaling pathways, including FAK, MAPK, and PI-3 K, which mediate the response of fibroblasts to mechanical stress. Secreted signals from diverse cell types have profound effects on phenotypic changes. In response to injury, the heart releases a wide range of cellular factors that trigger and exacerbate the phenotype in a paracrine manner. These secreted factors are implicated in various outcomes such as fibrosis, myofibroblast activation, collagen synthesis, calcification, hypertrophy, and inflammation. TGF-β: transforming growth factor-β; AT1R, type 1 angiotensin II receptor; ERK; extracellular-signal-regulated kinase; FAK, focal adhesion kinase; IL-11RA, IL-11 receptor subunit-α; MAPK, mitogen-activated protein kinase; MR, mineralocorticoid receptor; PI3K, phosphoinositide 3-kinase; TAK1; TGF-beta activated kinase 1, TGFβ-activated kinase 1; TGFβR1, TGFβ receptor type 1. PAK, p21-Activated kinases; NF-κB, The nuclear factor-kappaB; Dvl, Dishevelled; LRP5/6, low-density lipoprotein receptor-related protein; GSK3, glycogen synthase kinase 3; APC, adenomatous polyposis coli; CK1, casein kinase 1; TCF, T cell Factor