Endothelial-to-mesenchymal transition compromises vascular integrity to induce Myc-mediated metabolic reprogramming in kidney fibrosis.

Science Signaling
Sara LovisaRaghu Kalluri

Abstract

Endothelial-to-mesenchymal transition (EndMT) is a cellular transdifferentiation program in which endothelial cells partially lose their endothelial identity and acquire mesenchymal-like features. Renal capillary endothelial cells can undergo EndMT in association with persistent damage of the renal parenchyma. The functional consequence(s) of EndMT in kidney fibrosis remains unexplored. Here, we studied the effect of Twist or Snail deficiency in endothelial cells on EndMT in kidney fibrosis. Conditional deletion of Twist1 (which encodes Twist) or Snai1 (which encodes Snail) in VE-cadherin+ or Tie1+ endothelial cells inhibited the emergence of EndMT and improved kidney fibrosis in two different kidney injury/fibrosis mouse models. Suppression of EndMT limited peritubular vascular leakage, reduced tissue hypoxia, and preserved tubular epithelial health and function. Hypoxia, which was exacerbated by EndMT, resulted in increased Myc abundance in tubular epithelial cells, enhanced glycolysis, and suppression of fatty acid oxidation. Pharmacological suppression or epithelial-specific genetic ablation of Myc in tubular epithelial cells ameliorated fibrosis and restored renal parenchymal function and metabolic homeostasis. Together, t...Continue Reading

References

Jul 1, 1995·Circulation Research·L M Eisenberg, R R Markwald
Jul 30, 2003·The Journal of Biological Chemistry·Martin O LeonardCormac T Taylor
Jul 31, 2007·Nature Medicine·Elisabeth M ZeisbergRaghu Kalluri
Sep 18, 2007·Genesis : the Journal of Genetics and Development·You-Tzung ChenRichard R Behringer
Nov 27, 2007·The Journal of Clinical Investigation·Debra F HigginsVolker H Haase
Dec 29, 2007·The Journal of Pathology·T A Wynn
Aug 1, 2008·American Journal of Physiology. Renal Physiology·Kuniko KimuraYoshihiko Saito
Nov 7, 2008·Journal of the American Society of Nephrology : JASN·Elisabeth M ZeisbergRaghu Kalluri
Sep 22, 2009·American Journal of Respiratory Cell and Molecular Biology·Naozumi HashimotoYoshinori Hasegawa
Nov 26, 2010·Nature Medicine·Damian MediciBjorn R Olsen
Dec 3, 2010·American Journal of Physiology. Renal Physiology·David P BasileTimothy A Sutton
Dec 3, 2010·American Journal of Physiology. Cell Physiology·William W Wheaton, Navdeep S Chandel
Sep 29, 2011·The American Journal of Pathology·Florian RiederClaudio Fiocchi
Feb 7, 2012·Nature Medicine·Hikaru SugimotoRaghu Kalluri
Dec 25, 2012·Fibrogenesis & Tissue Repair·Dominique GuerrotChristos Chatziantoniou
Jan 22, 2013·Journal of the American Society of Nephrology : JASN·Volker H Haase
Jul 3, 2013·Nature Medicine·Valerie S LeBleuRaghu Kalluri
Jan 28, 2014·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Claudia CurciGiuseppe Grandaliano
Mar 14, 2014·Science Translational Medicine·Brian C CooleyManfred Boehm
Jun 5, 2014·Nature Communications·Zhao-Qiu WuStephen J Weiss
Nov 22, 2014·Investigative Ophthalmology & Visual Science·Jie LiJing Chen
Dec 24, 2014·Journal of the American Society of Nephrology : JASN·Sandhya XavierMichael S Goligorsky
May 23, 2015·Journal of the American Society of Nephrology : JASN·Yi-Chun Xu-DuboisAlexandre Hertig
Aug 28, 2015·Kidney International Supplements·Barbara J Ballermann, Marya Obeidat
Nov 1, 2015·The Journal of Clinical Investigation·Pei-Yu ChenMichael Simons
Nov 2, 2016·Journal of the American Society of Nephrology : JASN·Rongpei LanManjeri A Venkatachalam
Jun 2, 2016·Circulation Research·Marwa M MahmoudPaul C Evans
Nov 1, 2016·American Journal of Respiratory Cell and Molecular Biology·Tadanori MammotoAkiko Mammoto
Nov 3, 2016·Cancer Research·Li ZhangMichael Ittmann
Feb 10, 2017·Nature Communications·Elisabetta DejanaMichael Simons
Apr 5, 2017·Journal of Cellular and Molecular Medicine·Zijie WangMin Gu

❮ Previous
Next ❯

Citations

Jun 11, 2020·Science Signaling·Michael S Balzer, Katalin Susztak
Nov 6, 2020·Scientific Reports·Shujun ZhouQihe Xu
Jun 30, 2021·Trends in Molecular Medicine·Lilach O Lerman
Jun 30, 2021·Cellular and Molecular Life Sciences : CMLS·Zhenzhen LiXiaobing Li
Aug 28, 2021·International Journal of Molecular Sciences·Nina P JordanSimi Ali

❮ Previous
Next ❯

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.