The impact of aryl hydrocarbon receptor signaling on matrix metabolism: implications for development and disease.
The aryl hydrocarbon receptor (AhR) was identified as the receptor for polycyclic aromatic hydrocarbons and related compounds. However, novel data indicate that the AhR binds a variety of unrelated endogenous and exogenous compounds. Although AhR knockout mice demonstrate that this receptor has a role in normal development and physiology, the function of this receptor is still unclear. Recent evidence suggests that AhR signaling also alters the expression of genes involved in matrix metabolism, specifically the matrix metalloproteinases (MMPs). MMP expression and activity is critical to normal physiological processes that require tissue remodeling, as well as in mediating the progression of a variety of diseases. MMPs not only degrade structural proteins, but are also important mediators of cell signaling near or at the cell membrane through exposure of cryptic sites, release of growth factors, and cleavage of receptors. Therefore, AhR modulation of MMP expression and activity may be critical, not only in pathogenesis, but also in understanding the endogenous function of the AhR. In this review we will examine the data indicating a role for the AhR-signaling pathway in the regulation of matrix remodeling, and discuss potential molecular mechanisms.
Hillegass
Jedd M
JM
Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, 76 Lipman Dr., New Brunswick, NJ 08901, USA.
Murphy
Kyle A
KA
Villano
Caren M
CM
White
Lori A
LA
D000818:Animals; D004194:Disease; D006801:Humans; D020782:Matrix Metalloproteinases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014212:Tretinoin / Q000378:metabolism
D016328:NF-kappa B; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D014212:Tretinoin; D020782:Matrix Metalloproteinases