Hillegass Jedd M, Murphy Kyle A, Villano Caren M, White Lori A
Department of Biochemistry and Microbiology, Rutgers, The State University of New Jersey, 76 Lipman Dr., New Brunswick, NJ 08901, USA.
Biol Chem. 2006 Sep;387(9):1159-73. doi: 10.1515/BC.2006.144.
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.
芳烃受体（AhR）被确定为多环芳烃及相关化合物的受体。然而，新数据表明AhR可结合多种不相关的内源性和外源性化合物。尽管AhR基因敲除小鼠表明该受体在正常发育和生理过程中发挥作用，但其功能仍不清楚。最近的证据表明，AhR信号传导还会改变参与基质代谢的基因的表达，特别是基质金属蛋白酶（MMPs）。MMP的表达和活性对于需要组织重塑的正常生理过程以及介导多种疾病的进展至关重要。MMPs不仅能降解结构蛋白，还通过暴露隐蔽位点、释放生长因子和切割受体，在细胞膜附近或细胞膜处成为细胞信号传导的重要介质。因此，AhR对MMP表达和活性的调节可能不仅在发病机制中至关重要，而且对于理解AhR的内源性功能也至关重要。在本综述中，我们将研究表明AhR信号通路在基质重塑调节中作用的数据，并讨论潜在的分子机制。
