Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers
| العنوان: | Identification of VEGF Signaling Inhibition-Induced Glomerular Injury in Rats through Site-Specific Urinary Biomarkers |
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| المؤلفون: | Kenneth Kowalkowski, Keith B. Glaser, Wayne R. Buck, Yi Yang, Rita Ciurlionis, Eric A. G. Blomme, Daniel H. Albert |
| المصدر: | 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 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::210f677cdf88bcd6d72e8a4c2ff07611Test https://www.mdpi.com/1422-0067/22/23/12629Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....210f677cdf88bcd6d72e8a4c2ff07611 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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