A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling

Miret, Noelia; Rico-Leo, Eva M.; Pontillo, Carolina; Zotta, Elsa; Fernández-Salguero, Pedro M.; Randi, Andrea

doi:10.1016/j.taap.2017.09.012

Cited by 11 publications

(5 citation statements)

References 76 publications

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“…By screening 45 pathways, we identified that the cytoplasmic Kyn-Src-activated YAP and ERK pathways promoted CM proliferation and heart regeneration 45 – 47 . Consistently, AHR regulated these two pathways in mouse mammary glands and lung cancer cells 16 , 48 . Because of a high level of system L transporter in both CMs and endothelial cells, Kyn could freely transport between these two cells in vivo and in vitro.…”

Section: Discussionmentioning

confidence: 63%

Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis

et al. 2022

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Indoleamine 2,3 dioxygenase-1 (IDO1) catalyzes tryptophan-kynurenine metabolism in many inflammatory and cancer diseases. Of note, acute inflammation that occurs immediately after heart injury is essential for neonatal cardiomyocyte proliferation and heart regeneration. However, the IDO1-catalyzed tryptophan metabolism during heart regeneration is largely unexplored. Here, we find that apical neonatal mouse heart resection surgery led to rapid and consistent increases in cardiac IDO1 expression and kynurenine accumulation. Cardiac deletion of Ido1 gene or chemical inhibition of IDO1 impairs heart regeneration. Mechanistically, elevated kynurenine triggers cardiomyocyte proliferation by activating the cytoplasmic aryl hydrocarbon receptor-SRC-YAP/ERK pathway. In addition, cardiomyocyte-derived kynurenine transports to endothelial cells and stimulates cardiac angiogenesis by promoting aryl hydrocarbon receptor nuclear translocation and enhancing vascular endothelial growth factor A expression. Notably, Ahr deletion prevents indoleamine 2,3 dioxygenase -kynurenine–associated heart regeneration. In summary, increasing indoleamine 2,3 dioxygenase-derived kynurenine level promotes cardiac regeneration by functioning as an endogenous regulator of cardiomyocyte proliferation and cardiac angiogenesis.

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Section: Discussionmentioning

confidence: 63%

Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis

et al. 2022

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“…As previously described [ 12 ], MG development can be regarded as accelerated if the number of TEBs in the treated group is higher than that of the control at 3 weeks of age. Exposure to hexachlorobenzene (HCB) has been shown to increase the number of TEBs in C57BL/6 mice [ 56 ], which could increase the risk of breast cancer [ 57 – 59 ]. However, the opposite was observed in the present study and, thus, perinatal exposure to the High dose of POPs seemed to restrict MG development in 3-week-old female mice.…”

Section: Discussionmentioning

confidence: 99%

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

et al. 2021

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The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

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“…Previous results have shown that 0.05 µM HCB activates the AhR/c-Src/Smad3 axis in NMuMG cells, while AhR/c-Src is stimulated at 0.005 µM HCB [28,58]. Herein, we studied CPF action on these signaling pathways.…”

Section: Pesticide Action On Line-1 Mrna Expression and Role Of Ahr A...mentioning

confidence: 90%

“…The AhR and TGF-β1 signaling pathways are interrelated and regulate several common processes including cell proliferation, differentiation, migration, invasion, and apoptosis [25,26]. For instance, HCB exposure in breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG, promotes the phosphorylation of c-Src through AhR, leading to the activation of TGF-β1 signaling and an increase in cell migration and invasion [27,28].…”

Section: Introductionmentioning

confidence: 99%

AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

Miret

Zappia

Altamirano

et al. 2020

Biochemical Pharmacology

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A dioxin-like compound induces hyperplasia and branching morphogenesis in mouse mammary gland, through alterations in TGF-β1 and aryl hydrocarbon receptor signaling

Cited by 11 publications

References 76 publications

Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis

Kynurenine promotes neonatal heart regeneration by stimulating cardiomyocyte proliferation and cardiac angiogenesis

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice

AhR ligands reactivate LINE-1 retrotransposon in triple-negative breast cancer cells MDA-MB-231 and non-tumorigenic mammary epithelial cells NMuMG

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