Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway - PubMed (original) (raw)
doi: 10.1038/ki.2013.133. Epub 2013 May 1.
Claire Cerini, Laetitia Dou, Marion Sallée, Ariane Duval-Sabatier, Anneleen Pletinck, Raymond Calaf, Romaric Lacroix, Noémie Jourde-Chiche, Stéphane Poitevin, Laurent Arnaud, Raymond Vanholder, Philippe Brunet, Françoise Dignat-George, Stéphane Burtey
Affiliations
- PMID: 23636172
- DOI: 10.1038/ki.2013.133
Free article
Indolic uremic solutes increase tissue factor production in endothelial cells by the aryl hydrocarbon receptor pathway
Bertrand Gondouin et al. Kidney Int. 2013 Oct.
Free article
Abstract
In chronic kidney disease (CKD), uremic solutes accumulate in blood and tissues. These compounds probably contribute to the marked increase in cardiovascular risk during the progression of CKD. The uremic solutes indoxyl sulfate and indole-3-acetic acid (IAA) are particularly deleterious for endothelial cells. Here we performed microarray and comparative PCR analyses to identify genes in endothelial cells targeted by these two uremic solutes. We found an increase in endothelial expression of tissue factor in response to indoxyl sulfate and IAA and upregulation of eight genes regulated by the transcription factor aryl hydrocarbon receptor (AHR). The suggestion by microarray analysis of an involvement of AHR in tissue factor production was confirmed by siRNA inhibition and the indirect AHR inhibitor geldanamycin. These observations were extended to peripheral blood mononuclear cells. Tissue factor expression and activity were also increased by AHR agonist dioxin. Finally, we measured circulating tissue factor concentration and activity in healthy control subjects and in patients with CKD (stages 3-5d), and found that each was elevated in patients with CKD. Circulating tissue factor levels were positively correlated with plasma indoxyl sulfate and IAA. Thus, indolic uremic solutes increase tissue factor production in endothelial and peripheral blood mononuclear cells by AHR activation, evoking a 'dioxin-like' effect. This newly described mechanism of uremic solute toxicity may help understand the high cardiovascular risk of CKD patients.
Similar articles
- Mechanisms of tissue factor induction by the uremic toxin indole-3 acetic acid through aryl hydrocarbon receptor/nuclear factor-kappa B signaling pathway in human endothelial cells.
Addi T, Poitevin S, McKay N, El Mecherfi KE, Kheroua O, Jourde-Chiche N, de Macedo A, Gondouin B, Cerini C, Brunet P, Dignat-George F, Burtey S, Dou L. Addi T, et al. Arch Toxicol. 2019 Jan;93(1):121-136. doi: 10.1007/s00204-018-2328-3. Epub 2018 Oct 15. Arch Toxicol. 2019. PMID: 30324315 - Aryl Hydrocarbon Receptor Activation and Tissue Factor Induction by Fluid Shear Stress and Indoxyl Sulfate in Endothelial Cells.
Lano G, Laforêt M, Von Kotze C, Perrin J, Addi T, Brunet P, Poitevin S, Burtey S, Dou L. Lano G, et al. Int J Mol Sci. 2020 Mar 31;21(7):2392. doi: 10.3390/ijms21072392. Int J Mol Sci. 2020. PMID: 32244284 Free PMC article. - Aryl Hydrocarbon Receptor and Uremic Toxins from the Gut Microbiota in Chronic Kidney Disease Patients: Is There a Relationship between Them?
Brito JS, Borges NA, Anjos JSD, Nakao LS, Stockler-Pinto MB, Paiva BR, Cardoso-Weide LC, Cardozo LFMF, Mafra D. Brito JS, et al. Biochemistry. 2019 Apr 16;58(15):2054-2060. doi: 10.1021/acs.biochem.8b01305. Epub 2019 Apr 3. Biochemistry. 2019. PMID: 30912928 - Aryl Hydrocarbon Receptor Activation in Chronic Kidney Disease: Role of Uremic Toxins.
Brito JS, Borges NA, Esgalhado M, Magliano DC, Soulage CO, Mafra D. Brito JS, et al. Nephron. 2017;137(1):1-7. doi: 10.1159/000476074. Epub 2017 May 11. Nephron. 2017. PMID: 28490014 Review. - The aryl hydrocarbon receptor-activating effect of uremic toxins from tryptophan metabolism: a new concept to understand cardiovascular complications of chronic kidney disease.
Sallée M, Dou L, Cerini C, Poitevin S, Brunet P, Burtey S. Sallée M, et al. Toxins (Basel). 2014 Mar 4;6(3):934-49. doi: 10.3390/toxins6030934. Toxins (Basel). 2014. PMID: 24599232 Free PMC article. Review.
Cited by
- Increased Blood-Brain Barrier Permeability and Cognitive Impairment in Patients With ESKD.
Bobot M, Guedj E, Resseguier N, Faraut J, Garrigue P, Nail V, Hache G, Gonzalez S, McKay N, Vial R, Bouchouareb D, Lano G, Jourde-Chiche N, Duval-Sabatier A, Guilaume F, Guillet B, Burtey S. Bobot M, et al. Kidney Int Rep. 2024 Jul 20;9(10):2988-2995. doi: 10.1016/j.ekir.2024.07.021. eCollection 2024 Oct. Kidney Int Rep. 2024. PMID: 39430169 Free PMC article. - In laying hens, chronic heat stress-induced renal fibrosis is potentially promoted by indoxyl sulfate.
Nanto-Hara F, Ohtsu H. Nanto-Hara F, et al. Sci Rep. 2024 Oct 5;14(1):23213. doi: 10.1038/s41598-024-75066-0. Sci Rep. 2024. PMID: 39369114 Free PMC article. - The gut microbiota in thrombosis.
Khuu MP, Paeslack N, Dremova O, Benakis C, Kiouptsi K, Reinhardt C. Khuu MP, et al. Nat Rev Cardiol. 2024 Sep 17. doi: 10.1038/s41569-024-01070-6. Online ahead of print. Nat Rev Cardiol. 2024. PMID: 39289543 Review. - Natural antagonistic flavones for AhR inhibit indoxyl sulfate-induced inflammatory gene expression in vitro and renal pathological damages in vivo.
Iwashima T, Takemura Y, Kishimoto Y, Ono C, Watanabe A, Iida K. Iwashima T, et al. Food Nutr Res. 2024 Jul 31;68. doi: 10.29219/fnr.v68.10032. eCollection 2024. Food Nutr Res. 2024. PMID: 39113916 Free PMC article. - A Historical Perspective on Uremia and Uremic Toxins.
Meijers B, Zadora W, Lowenstein J. Meijers B, et al. Toxins (Basel). 2024 May 15;16(5):227. doi: 10.3390/toxins16050227. Toxins (Basel). 2024. PMID: 38787079 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources