Abstract
Chronic kidney disease (CKD) is characterized by renal dysfunction, which is a common feature of other major diseases, such as hypertension and diabetes. Unilateral ureteral obstruction (UUO) has been used as a model of CKD in experimental animals and consists of total obstruction of one kidney ureter. The UUO decreases renal blood flow, which promotes the synthesis of renin in the juxtaglomerular apparatus, the first step in renin–angiotensin system (RAS) cascade. RAS induces inflammation and remodeling, along with reduced renal function. However, it remains unknown whether intrarenal RAS (iRAS) is activated in early stages of CKD. Our objective was to characterize different iRAS components in the renal cortex and in the medulla in an early phase of UUO. Male C57BL/6 mice (8–12 weeks old) were subjected to UUO in the left kidney, or to sham surgery, and were euthanized after 7 days (n = 5/group). Renal function, renal inflammatory/remodeling processes, and iRAS expression were evaluated. UUO increased plasma creatinine, right renal hypertrophy (9.08 ± 0.31, P < 0.05 vs. Sham), and tubular dilatation in the left kidney cortex (42.42 ± 8.19µm, P < 0.05 vs. Sham). This correlated with the increased mRNA of IL-1β (1.73 ± 0.14, P < 0.01 vs. Sham, a pro-inflammatory cytokine) and TGF-β1 (1.76 ± 0.10, P < 0.001 vs. Sham, a pro-fibrotic marker). In the renal cortex of the left kidney, UUO increased the mRNA and protein levels of renin (in 35% and 28%, respectively, P < 0.05 vs. Sham). UUO decreased mRNA and protein levels for the (pro)renin receptor in the renal medulla (0.67 ± 0.036 and 0.88 ± 0.028, respectively, P < 0.05 vs. Sham). Our results suggest that modulation of iRAS components depends on renal localization and occurs in parallel with remodeling and pro-inflammatory/pro-fibrotic mechanisms.
Highlights
Chronic kidney disease (CKD) is a worldwide health problem closely linked to other major diseases (Tonelli et al, 2015) that is difficult to diagnose and affects around 10% of the population (De Nicola and Zoccali 2016)
As the renal remodeling induced by 7 days of ureteral obstruction (UUO) was not equal in the renal cortex and in the medulla, we studied the levels of intrarenal RAS (iRAS) components separately
By using an experimental CKD model that promotes renal inflammation driving to fibrosis, we have characterized different elements of iRAS in the cortex and in renal medulla
Summary
Chronic kidney disease (CKD) is a worldwide health problem closely linked to other major diseases (Tonelli et al, 2015) that is difficult to diagnose and affects around 10% of the population (De Nicola and Zoccali 2016). Evidential structural abnormalities in CKD are characterized by glomerulosclerosis, tubular atrophy, and tubulo-interstitial fibrosis (Menon and Ross 2016), three conditions that drive nephrons to deterioration and to irreversible renal failure. It has been demonstrated that UUO increases interstitial capillary permeability (Yamaguchi et al, 2012) and the levels of IL-1-linked cytokines and transforming growth factor-β1 (TGF-β1), which correlate with the recruitment of inflammatory mononuclear cells (Eddy and Neilson 2006; Chi et al, 2017). The UUO surgery in rodents can be used as an experimental model for studying the early (inflammatory, 7 days) (Ucero et al, 2014) and/or consolidated (fibrotic, 14 days) stage of CKD (MartínezKlimova et al, 2019)
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
