Matrix-dependent perturbation of TGFβ signaling and disease.
Transforming growth factor beta (TGFβ) is a multipotent cytokine that is sequestered in the extracellular matrix (ECM) through interactions with a number of ECM proteins. The ECM serves to concentrate latent TGFβ at sites of intended function, to influence the bioavailability and/or function of TGFβ activators, and perhaps to regulate the intrinsic performance of cell surface effectors of TGFβ signal propagation. The downstream consequences of TGFβ signaling cascades in turn provide feedback modulation of the ECM. This review covers recent examples of how genetic mutations in constituents of the ECM or TGFβ signaling cascade result in altered ECM homeostasis, cellular performance and ultimately disease, with an emphasis on emerging therapeutic strategies that seek to capitalize on this refined mechanistic understanding.
Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. jefferson.doyle@jhmi.edu
Jefferson J
JJ
Doyle
Elizabeth E
EE
Gerber
Harry C
HC
Dietz
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D000071837:Fibrillins; D006706:Homeostasis; D006801:Humans; D016023:Integrins / Q000378:metabolism; D008382:Marfan Syndrome / Q000378:metabolism; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D015398:Signal Transduction; D013577:Syndrome; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D016207:Cytokines; D000071837:Fibrillins; D016023:Integrins; D008840:Microfilament Proteins; D016212:Transforming Growth Factor beta