RGD Reference Report - Avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) plays a role in renal microvascular pathophysiology in the Dahl salt-sensitive rat. - Rat Genome Database

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Avian erythroblastosis virus E26 oncogene homolog-1 (ETS-1) plays a role in renal microvascular pathophysiology in the Dahl salt-sensitive rat.

Authors: Feng, Wenguang  Guan, Zhengrong  Xing, Dongqi  Li, Xingsheng  Ying, Wei-Zhong  Remedies, Colton E  Inscho, Edward W  Sanders, Paul W 
Citation: Feng W, etal., Kidney Int. 2020 Mar;97(3):528-537. doi: 10.1016/j.kint.2019.09.025. Epub 2019 Oct 22.
RGD ID: 150429812
Pubmed: (View Article at PubMed) PMID:31932071
DOI: Full-text: DOI:10.1016/j.kint.2019.09.025

Prior studies reported that haploinsufficiency of the transcription factor ETS-1 is renoprotective in Dahl salt-sensitive rats, but the mechanism is unclear. Here, we tested whether ETS-1 is involved in hypertension-induced renal microvascular pathology and autoregulatory impairment. Hypertension was induced in salt-sensitive rats and salt-sensitive rats that are heterozygous with 1 wild-type or reference allele of Ets1 (SSEts1+/-) by feeding a diet containing 4% sodium chloride for 1 week. Increases in blood pressure did not differ. However, phosphorylated ETS-1 increased in afferent arterioles of hypertensive salt-sensitive rats, but not in hypertensive SSEts1+/- rats. Afferent arterioles of hypertensive salt-sensitive rats showed increased monocyte chemotactic protein-1 expression and infiltration of CD68 positive monocytes/macrophages. Isolated kidney microvessels showed increased mRNA expression of vascular cell adhesion molecule, intercellular adhesion molecule, P-selectin, fibronectin, transforming growth factor-β, and collagen I in hypertensive salt-sensitive rats compared with hypertensive SSEts1+/- rats. Using the in vitro blood-perfused juxtamedullary nephron preparation, pressure-mediated afferent arteriolar responses were significantly blunted in hypertensive salt-sensitive rats compared to hypertensive SSEts1+/- rats. Over a 65-170 mm Hg pressure range tested baseline arteriolar diameters averaged 15.1 μm and remained between 107% and 89% of baseline diameter in hypertensive salt-sensitive rats vs. 114% and 73% in hypertensive SSEts1+/- rats (significantly different). Thus, ETS-1 participates in renal arteriolar pathology and autoregulation and thereby is involved in hypertension-mediated kidney injury in salt-sensitive rats.



Gene Ontology Annotations    

Biological Process

Cellular Component
nucleus  (IDA)

Phenotype Annotations    

Mammalian Phenotype
Objects Annotated

Genes (Rattus norvegicus)
Ets1  (ETS proto-oncogene 1, transcription factor)
Ets1em1Mcwi  (v-ets erythroblastosis virus E26 oncogene homolog 1 (avian); zinc finger nuclease induced mutant 1, Medical College of Wisconsin)

Strains
SS-Ets1em1Mcwi-/+  (SS-Ets1em1Mcwi-/Ets1em1Mcwi+)

Objects referenced in this article
Strain SS-Ets1em1Mcwi+/+ SS-Ets1em1Mcwi+/Ets1em1Mcwi+ Rattus norvegicus
Strain SS-Ets1em1Mcwi null Rattus norvegicus

Additional Information