Tryptophan Metabolites Regulate Neuropentraxin 1 Expression in Endothelial Cells

Romain Vial (1) , Stéphane Poitevin (2) , Nathalie Mckay (2) , Stéphane Burtey (2) , Claire Cerini (2)

1 LA CONCEPTION - Hôpital de la Conception [CHU - APHM]
2 C2VN - Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research

In patients with chronic kidney disease (CKD) and in animal models of CKD, the transcription factor Aryl Hydrocabon Receptor (AhR) is overactivated. In addition to the canonical AhR targets constituting the AhR signature, numerous other genes are regulated by this factor. We identified neuronal pentraxin 1 (NPTX1) as a new AhR target. Belonging to the inflammatory protein family, NPTX1 seems of prime interest regarding the inflammatory state observed in CKD. Endothelial cells were exposed to tryptophan-derived toxins, indoxyl sulfate (IS) and indole-3-acetic acid (IAA). The adenine mouse model of CKD was used to analyze NPTX1 expression in the burden of uremia. NPTX1 expression was quantified by RT-PCR and western blot. AhR involvement was analyzed using silencing RNA. We found that IS and IAA upregulated NPTX1 expression in an AhR-dependent way. Furthermore, this effect was not restricted to uremic indolic toxins since the dioxin 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) do the same. In CKD mice, NPTX1 expression was increased in the aorta. Therefore, NPTX1 is a new target of AhR and further work is necessary to elucidate its exact role during CKD.

Mots clés: aryl hydrocarbon receptor; indolic uremic toxins; indoxyl sulfate; indole-3-acetic acid; neuropentraxin 1

Domaines: Sciences du Vivant [q-bio]

Romain Vial, Stéphane Poitevin, Nathalie Mckay, Stéphane Burtey, Claire Cerini. Tryptophan Metabolites Regulate Neuropentraxin 1 Expression in Endothelial Cells. International Journal of Molecular Sciences, 2022, 23 (4), pp.2369. ⟨10.3390/ijms23042369⟩. ⟨hal-03685840⟩