TGFbeta, cardiac fibroblasts, and the fibrotic response

The cytokine transforming growth factor beta (TGFbeta) is a major contributor to fibrogenic responses both in vitro and in vivo. TGFbeta possesses many functions; thus, broadly targeting TGFbeta signaling as an anti-fibrotic approach is anticipated to be problematic. Recent experiments, however, have begun to elucidate the signaling pathways through which TGFbeta activates a fibrotic program. This review critically evaluates the evidence supporting TGFbeta as a pro-fibrotic cytokine, with special attention to cardiac fibrosis, and suggests several possible points for selective drug intervention to combat chronic fibrotic disease.