RAGE-aptamer attenuates deoxycorticosterone acetate/salt-induced renal injury in mice

Autor: Yosuke Nakayama, Miyuki Yokoro, Sakuya Ito, Kensei Taguchi, Ryotaro Ando, Takanori Matsui, Yuichiro Higashimoto, Seiji Ueda, Kei Fukami, Craig R. Brooks, Nana Yamada-Obara, Yusuke Kaida, Goh Kodama, Katsuhiko Asanuma, Seiya Okuda, Sho-ichi Yamagishi
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Glycation End Products
Advanced
Male
endocrine system diseases
Kidney Glomerulus
Receptor for Advanced Glycation End Products
lcsh:Medicine
Blood Pressure
030204 cardiovascular system & hematology
Acetates
medicine.disease_cause
chemistry.chemical_compound
Mice
0302 clinical medicine
Mineralocorticoid receptor
Glycation
Receptor
lcsh:Science
Aldosterone
Mice
Knockout
Kidney
Multidisciplinary
Nitrotyrosine
Acute Kidney Injury
medicine.anatomical_structure
Hypertension
cardiovascular system
Kidney Diseases
medicine.medical_specialty
Article
03 medical and health sciences
Desoxycorticosterone Acetate
Internal medicine
medicine
Animals
cardiovascular diseases
Sodium Chloride
Dietary
business.industry
lcsh:R
nutritional and metabolic diseases
Mice
Inbred C57BL
030104 developmental biology
Endocrinology
Receptors
Mineralocorticoid
chemistry
Tubulointerstitial fibrosis
lcsh:Q
business
human activities
Oxidative stress
Aptamers
Peptide
Zdroj: Scientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
Scientific Reports
ISSN: 2045-2322
Popis: The mineralocorticoid receptor (MR) and its downstream signaling play an important role in hypertensive renal injury. The interaction of advanced glycation end products (AGE) with their receptor (RAGE) is involved in the progression of renal disease. However, the pathological crosstalk between AGE–RAGE axis and MR system in kidney derangement remains unclear. We screened DNA-aptamer directed against RAGE (RAGE-apt) in vitro and examined its effects on renal injury in uninephrectomized deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mice. RAGE, GTP-bound Rac-1 (Rac1), and MR were co-localized in the podocytes of DOCA mice. The deletion of RAGE gene significantly inhibited mesangial matrix expansion and tubulointerstitial fibrosis in DOCA mice, which was associated with the reduction of glomerular oxidative stress, MR, Rac1, and urinary albumin excretion (UAE) levels. RAGE-apt attenuated the increase in carboxymethyllysine (CML), RAGE, nitrotyrosine, Rac1, and MR levels in the kidneys and reduced UAE in DOCA mice. Aldosterone (Aldo) increased nitrotyrosine, CML, and RAGE gene expression in murine podocytes, whereas CML stimulated MR and Rac1 levels, which were blocked by RAGE-apt. The present study indicates the crosstalk between the AGE–RAGE axis and Aldo–MR system, suggesting that RAGE-apt may be a novel therapeutic tool for the treatment of MR-associated renal diseases.
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje