Dataset Information

(Pro)renin receptor antagonist PRO20 attenuates nephrectomy-induced nephropathy in rats via inhibition of intrarenal RAS and Wnt/β-catenin signaling.

ABSTRACT:

Introduction

(Pro)renin receptor has emerged as a new member of the renin-angiotensin system implicated in the pathogenesis of chronic kidney disease (CKD). Herein we report characterization of the therapeutic potential of (pro)renin receptor (PRR) antagonist PRO20 in 5/6 nephrectomy (5/6Nx) rats.

Methods

Male Wistar rats underwent 5/6Nx followed by treatment with vehicle or received daily injections of a PRR inhibitor PRO20 (700 μg/kg) via the 3 s.c. Sham group served as a control.

Results

As compared with the sham control, the 5/6Nx rats exhibited significant increases in proteinuria, glomerulosclerosis, tubular injury, and interstitial inflammation in the remnant kidneys. Treatment with PRO20 significantly attenuated these abnormalities, as evidenced by reduced expression of fibronectin, α-SMA, collagen 1, TGF-β1, IL-6, IL-8, IL-1β, MCP-1 and increased expression of E-cadherin. Increased urinary/renal levels of renin activity, angiotensinogen (AGT), and Angiotensin II (Ang II) by 5/6Nx, which were all ameliorated by PRO20. Renal PRR, the secreted proteolytic fragment of PRR (sPRR) in renal and urinary, were all elevated in 5/6Nx rats. Moreover, our results revealed that renal Wnt3A and β-catenin expression were upregulated during 5/6Nx, which were all attenuated by PRO20.

Conclusions

Overall we conclude that in vivo antagonism of PRR with PRO20 will improve 5/6Nx-induced CKD mainly through inhibition of intrarenal RAS and Wnt/β-catenin signaling pathway.

SUBMITTER: Wang Y

PROVIDER: S-EPMC8165733 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo evaluate the feasibility and efficacy of intraoperative ultrasonography in laparoscopic partial nephrectomy (LPN) for intrarenal tumors.Patients and methodsAll patients who underwent LPN for renal tumors in our institution from January 2010 to October 2016 were assessed retrospectively. Patients were divided into two groups, the first with totally intrarenal tumors (TIT group), defined as a solid renal mass with no exophytic element on both preoperative and intraoperative evaluations, and the second with exophytic tumors (control group). General information and perioperative data of the two groups were compared, including tumor characteristics, operative time, estimated blood loss, warm ischemia time and pathological findings. Intraoperative laparoscopic ultrasonography (ILUS) was used to precisely locate and delineate the TIT border, as well as seeking for other suspected lesions.ResultsWe identified 583 patients who underwent LPN in our center, including 46 in the TIT and 537 in the control group. All patients in the TIT group were evaluated by ILUS, and all TIT procedures were successfully performed with only one conversion to open surgery. The mean tumor sizes in the TIT and control groups were 2.42 ± 0.46 cm and 3.29 ± 1.43 cm (p < 0.001), respectively. The TIT group's R.E.N.A.L. nephrometry score was higher than that of the control group (median 8.5 vs 6.0, p < 0.001), and their mean operation times were 127.2 ± 16.0 min and 120.1 ± 19.2 min, respectively. Mean estimated blood loss was higher in the TIT than in the control group (161.3 ml vs 136.6 ml, p = 0.003). Mean warm ischemia time differed in the TIT and control groups (22.2 ± 6.4 vs 20.6 ± 4.7 min, p = 0.105), but not significantly. Rates of open conversion and positive margins, as well as rates of major postoperative complications, pathological findings, and 1-month changes in renal function, were similar in the two groups.ConclusionIntraoperative ultrasonography is technically feasible in patients undergoing LPN for TITs. This method may reduce the need for radical nephrectomy in patients with endogenic renal masses.