Skip to main content
. Author manuscript; available in PMC: 2017 Feb 1.
Published in final edited form as: J Mol Cell Cardiol. 2015 Dec 22;91:52–60. doi: 10.1016/j.yjmcc.2015.12.016

Figure 2. Major signaling pathways that promote fibroblast activation.

Figure 2

Multiple pathways converge on the myofibroblast phenotype. Mechanical stress or ligand mediated receptor activation can induce TGFβ signaling, GPCR activation, or calcium influx. TGFβ signaling plays a central role where the canonical arm results in nuclear localization of SMAD2/3/4. Inhibitory SMADs 6/7 or KLF15 can block SMAD2/3/4-dependent transcription whereas angiotensin/KLF5 signaling can enhance canonical TGFβ signaling. Non-canonical TGFβ signaling not only promotes MAPK/p38/JNK/ERK-dependent transcription, but can feed into the Rho/ROCK signaling pathway to promote MRTF nuclear localization. Rho/ROCK can also be activated by G-protein coupled receptors (GPCRs). Finally, mechanical tension can also disrupt β-catenin localization in the adherens junctions to prime the cell for further stimulation or cause calcium influx which activates calcineurin/NFAT signaling.