Indoxyl Sulfate Stimulates Angiogenesis by Regulating Reactive Oxygen Species Production via CYP1B1

Toxins
Jiayi PeiCaroline Cheng

Abstract

Indoxyl sulfate (IS) is an accumulative protein-bound uremic toxin found in patients with kidney disease. It is reported that IS impairs the vascular endothelium, but a comprehensive overview of all mechanisms active in IS-injury currently remains lacking. Here we performed RNA sequencing in human umbilical vein endothelial cells (HUVECs) after IS or control medium treatment and identified 1293 genes that were affected in a IS-induced response. Gene enrichment analysis highlighted pathways involved in altered vascular formation and cell metabolism. We confirmed these transcriptome profiles at the functional level by demonstrating decreased viability and increased cell senescence in response to IS treatment. In line with the additional pathways highlighted by the transcriptome analysis, we further could demonstrate that IS exposure of HUVECs promoted tubule formation as shown by the increase in total tubule length in a 3D HUVECs/pericytes co-culture assay. Notably, the pro-angiogenic response of IS and increased ROS production were abolished when CYP1B1, one of the main target genes that was highly upregulated by IS, was silenced. This observation indicates IS-induced ROS in endothelial cells is CYP1B1-dependent. Taken together,...Continue Reading

References

Dec 2, 2000·The American Journal of Medicine·K A Nath, S M Norby
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·G I MurrayM D Burke
Apr 5, 2003·Kidney International·Raymond VanholderUNKNOWN European Uremic Toxin Work Group (EUTox)
May 6, 2003·Proceedings of the National Academy of Sciences of the United States of America·Takashi MoriguchiMasayuki Yamamoto
Nov 5, 2003·Biopharmaceutics & Drug Disposition·Tsuneo DeguchiMasaki Otagiri
Mar 16, 2004·Cancer Treatment and Research·Sybill Patan
Jun 23, 2004·Advances in Experimental Medicine and Biology·Ram K Sindhu, Nosratola D Vaziri
Jul 29, 2004·British Journal of Cancer·M C E McFadyenG I Murray
Sep 30, 2005·Toxicological Sciences : an Official Journal of the Society of Toxicology·Rushang D PatelGary H Perdew
Sep 6, 2006·Experimental Cell Research·Togo Ikuta, Kaname Kawajiri
Apr 4, 2007·Journal of Thrombosis and Haemostasis : JTH·L DouP Brunet
Feb 27, 2008·Renal Failure·Narisa FutrakulKavi Ratanabanangkoon
Apr 15, 2008·Cancer Letters·Masuko Ushio-Fukai, Yoshimasa Nakamura
Nov 27, 2008·Kidney International. Supplement·Victoria CachofeiroJosé Luño
Apr 1, 2009·Laboratory Investigation; a Journal of Technical Methods and Pathology·Rushang D PatelGary H Perdew
May 26, 2009·Nucleic Acids Research·Jing ChenAnil G Jegga
Sep 30, 2010·Clinical Journal of the American Society of Nephrology : CJASN·Mina YuDuk-Hee Kang
Oct 4, 2013·American Journal of Physiology. Cell Physiology·Tammy L PalenskiNader Sheibani
Oct 8, 2013·PloS One·Simona AdessoStefania Marzocco
Dec 5, 2013·Blood·Young-Woong Kim, Tatiana V Byzova
Jan 15, 2014·Carcinogenesis·Katiuscia DallaglioAdriana Albini
Apr 15, 2014·Journal of Atherosclerosis and Thrombosis·Masayuki KoizumiToshisuke Morita
Oct 29, 2014·Journal of the American Society of Nephrology : JASN·Gerald SchulmanMiho Shimizu
Nov 29, 2014·International Journal of Nephrology·Takeo EdamatsuYoshiharu Itoh
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders
Aug 5, 2015·Nephrology·Robert J EllisChristudas Morais
Jan 30, 2016·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Wei WangHaichang Huang
Feb 18, 2016·Kidney International·Szu-Chun HungDer-Cherng Tarng
May 1, 2015·Kidney Diseases·Shinji TanakaMasaomi Nangaku
Oct 30, 2016·Hemodialysis International·Xiao TanXiaoqiang Ding
Dec 6, 2016·Toxins·Sheldon C Leong, Tammy L Sirich
Jul 8, 2017·Nutrients·Joanne M Dennis, Paul K Witting

❮ Previous
Next ❯

Citations

Jun 25, 2020·Toxins·Regiane Stafim da CunhaAndréa Emilia Marques Stinghen
Jan 29, 2021·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Griet GlorieuxFrancis Verbeke
Jan 7, 2021·American Journal of Physiology. Cell Physiology·Zachary R SalyersTerence E Ryan
Nov 14, 2020·Clinical Science·Alexa N CarreraBeshay N Zordoky
May 20, 2021·Antioxidants & Redox Signaling·Thomas EbertPaul G Shiels

❮ Previous
Next ❯

Datasets Mentioned

BETA
GSE132410

Methods Mentioned

BETA
RNA-seq
transfection
RNAseq
FCS

Software Mentioned

GSEA
AngioSys
GraphPad
ToppFun
ToppGene Suite
GraphPad Prism
Slidebook

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.