Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers

Autor: Kenneth Kowalkowski, Keith B. Glaser, Wayne R. Buck, Yi Yang, Rita Ciurlionis, Eric A. G. Blomme, Daniel H. Albert
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Male
Vascular Endothelial Growth Factor A
Pathology
medicine.medical_specialty
Urinalysis
QH301-705.5
Urinary system
Podocyte foot
Laser Capture Microdissection
Glomerulus (kidney)
Article
Catalysis
Rats
Sprague-Dawley
Inorganic Chemistry
chemistry.chemical_compound
Albumins
Animals
Medicine
urinary biomarkers
Physical and Theoretical Chemistry
Biology (General)
Protein Kinase Inhibitors
Molecular Biology
QD1-999
Spectroscopy
Laser capture microdissection
vascular endothelial growth factor
glomerular injury
medicine.diagnostic_test
business.industry
Organic Chemistry
Cancer
General Medicine
medicine.disease
Rats
Computer Science Applications
Vascular endothelial growth factor
Disease Models
Animal
Chemistry
Receptors
Vascular Endothelial Growth Factor
medicine.anatomical_structure
chemistry
Kidney Diseases
Signal transduction
beta 2-Microglobulin
business
Biomarkers
Signal Transduction
Zdroj: International Journal of Molecular Sciences, Vol 22, Iss 12629, p 12629 (2021)
International Journal of Molecular Sciences
International Journal of Molecular Sciences; Volume 22; Issue 23; Pages: 12629
ISSN: 1661-6596
1422-0067
Popis: Cancer therapies targeting the vascular endothelial growth factor (VEGF) signaling pathway can lead to renal damage by disrupting the glomerular ultrafiltration apparatus. The objective of the current study was to identify sensitive biomarkers for VEGF inhibition-induced glomerular changes in rats. Male Sprague-Dawley rats were administered an experimental VEGF receptor (VEGFR) inhibitor, ABT-123, for seven days to investigate the correlation of several biomarkers with microscopic and ultrastructural changes. Glomeruli obtained by laser capture microdissection were also subjected to gene expression analysis to investigate the underlying molecular events of VEGFR inhibition in glomerulus. ABT-123 induced characteristic glomerular ultrastructural changes in rats, including fusion of podocyte foot processes, the presence of subendothelial electron-dense deposits, and swelling and loss of fenestrations in glomerular endothelium. The subtle morphological changes cannot be detected with light microscopy or by changes in standard clinical chemistry and urinalysis. However, urinary albumin increased 44-fold as early as Day three. Urinary β2-microglobulin levels were also increased. Other urinary biomarkers that are typically associated with tubular injury were not significantly impacted. Such patterns in urinary biomarkers can provide valuable diagnostic insight to VEGF inhibition therapy-induced glomeruli injuries.
Databáze: OpenAIRE
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