Dioxin Receptor Deficiency Impairs Angiogenesis by a Mechanism Involving VEGF-A Depletion in the Endothelium and Transforming Growth Factor-β Overexpression in the Stroma

The Dioxin receptor modulates Caveolin-1 mobilization during directional migration: role of cholesterol

“…Previous work has shown that the AhR-target gene Cyp1a1 is induced after suspension of human keratinocytes, mouse Hepa1 cells and 10T1/2 fibroblasts [5,6], suggesting that AhR is activated following the disruption of cell-cell and cellsubstratum interactions. In agreement, AhR knock-out altered positioning and axon migration of neuronal cells in the invertebrate C. elegans [7] and reduced migration of murine fibroblasts [8][9][10] and endothelial cells [11]. Such migration-related functions of AhR can be induced by TCDD in human hepatoma HepG2 [12] and human breast tumor MCF-7 [13] cells or by receptor knock-out in primary keratinocytes [14].…”

Dioxin Receptor Expression Inhibits Basal and Transforming Growth Factor β-induced Epithelial-to-mesenchymal Transition

“…After 5 days of culture, medium was removed, and clones were washed in PBS, stained for 10 min with 0.5% (w/v) crystal violet, and counted. Clone formation in three dimensions (3-D) was analyzed by growing each cell line on Matrigel as described (11). Briefly, 5 ϫ 10 3 sh-AhR, CA-AhR, or EV NMuMG cells were seeded on Matrigel plugs for 3 days in complete medium.…”

“…Contrary to mesenchymal fibroblasts, AhR knockout in epidermal keratinocytes increases their motility and migration both in vitro and in vivo (10). In additional cell types such as primary mouse endothelial cells (11) and CD4 Ϫ CD8 Ϫ thymocytes (4,12), AhR activation promoted cell migration to newly formed blood vessels and to the spleen, respectively. The fact that AhR depletion increased primary keratinocytes migration and improved wound healing in vivo led us to suggest that AhR could be involved in the epithelial-to-mesenchymal transition (EMT).…”

Aryl Hydrocarbon Receptor Antagonism Attenuates Growth Factor Expression, Proliferation, and Migration in Fibroblast-Like Synoviocytes from Patients with Rheumatoid Arthritis

“…The release of VEGF and other growth factors enhances angiogenesis in inflamed synovial tissue, and thus elevated serum growth factor levels can serve as an indicator of RA severity. The fact that the AHR actively enhances IL1B, IL6, and VEGF secretion in RA-FLS, coupled with the fact that a recognized treatment for RA is an anti-IL6 receptor monoclonal antibody that lowers serum VEGF levels, suggests that using an AHR antagonist as a therapeutic treatment is worthy of further consideration (Lee et al, 2001;Nakahara et al, 2003;Roman et al, 2009;DiNatale et al, 2010b). High levels of cytokines and chemokines in synovial fluid transform FLS to undergo proliferation, forming a pannus tissue, which further secretes more cytokines and growth factors (Firestein, 1996).…”