Serum Soluble (Pro)Renin Receptor Levels in Maintenance Hemodialysis Patients

Amari, Yoshifumi; Morimoto, Satoshi; Nakajima, Fumitaka; Ando, Takashi; Ichihara, Atsuhiro

doi:10.1371/journal.pone.0158068

Cited by 20 publications

(25 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…g ., mesangial cells and podocytes) [ 36 , 37 ], in accordance with our current and previous data showing that s(P)RR protein levels were higher in the plasma than in the eye of patients with PDR [ 4 ]. Taken together with the following piles of evidence including the in vitro induction of (P)RR in glucose-stimulated renal cells [ 36 , 37 ], the in vivo expression of (P)RR in the kidney of patients and animals with diabetic nephropathy [ 47 , 48 ], the systemic elevation of s(P)RR in patients with kidney dysfunction and failure [ 13 , 14 , 16 , 20 ], and the significant association of s(P)RR with renal dysfunction parameters ( Fig 2 ); the currently observed increase in plasma s(P)RR levels in patients with PDR may have resulted mainly from renal rather than retinal production.…”

Section: Discussionmentioning

confidence: 99%

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy

et al. 2017

View full text Add to dashboard Cite

(Pro)renin receptor [(P)RR], a new component of the tissue renin-angiotensin system (RAS), plays a crucial role in inflammation and angiogenesis in the eye, thus contributing to the development of proliferative diabetic retinopathy (PDR). In this study, we investigated systemic factors related to plasma levels of soluble form of (P)RR [s(P)RR] in patients with PDR. Twenty type II diabetic patients with PDR and 20 age-matched, non-diabetic patients with idiopathic macular diseases were enrolled, and plasma levels of various molecules were measured by enzyme-linked immunosorbent assays. Human retinal microvascular endothelial cells were stimulated with several diabetes-related conditions to evaluate changes in gene expression using real-time quantitative PCR. Of various systemic parameters examined, the PDR patients had significantly higher blood sugar and serum creatinine levels than non-diabetic controls. Protein levels of s(P)RR, prorenin, tumor necrosis factor (TNF)-α, complement factor D (CFD), and leucine-rich α-2-glycoprotein 1 (LRG1) significantly increased in the plasma of PDR subjects as compared to non-diabetes, with positive correlations detected between s(P)RR and these inflammatory molecules but not prorenin. Estimated glomerular filtration rate and serum creatinine were also correlated with plasma s(P)RR, but not prorenin, levels. Among the inflammatory molecules correlated with s(P)RR in the plasma, TNF-α, but not CFD or LRG1, application to retinal endothelial cells upregulated the mRNA expression of (P)RR but not prorenin, while stimulation with high glucose enhanced both (P)RR and prorenin expression. These findings suggested close relationships between plasma s(P)RR and diabetes-induced factors including chronic inflammation, renal dysfunction, and hyperglycemia in patients with PDR.

show abstract

Section: Discussionmentioning

confidence: 99%

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Besides intraocular environments, s(P)RR levels were elevated in the serum or plasma of patients with several disorders, such as hypertension, obesity, preeclampsia, and kidney and heart failure [36][37][38][39][40][41][42] . In the plasma of patients with PDR as well, we showed elevated s(P)RR, renin and activated prorenin protein levels, so as to investigate systemic factors related to plasma levels of these RAS-initiators in patients with PDR 43 .…”

Section: Soluble (Pro)renin Receptor In Plasma Of Patients With Diabementioning

confidence: 99%

(Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy

Kanda

Ishida

2018

J of Diabetes Invest

View full text Add to dashboard Cite

The renin-angiotensin system (RAS), a crucial regulator of systemic blood pressure (circulatory RAS), plays distinct roles in pathological angiogenesis and inflammation in various organs (tissue RAS), such as diabetic microvascular complications. Using ocular clinical samples and animal disease models, we elucidated molecular mechanisms in which tissue RAS excites the expression of vascular endothelial growth factor (VEGF)-A responsible for retinal inflammation and angiogenesis, the two major pathological events in diabetic retinopathy (DR). Furthermore, we showed the involvement of (pro)renin receptor [(P)RR] in retinal RAS activation and its concurrent intracellular signal transduction (e.g., extracellular signal-regulated kinase); namely, the (P)RR-induced dual pathogenic bioactivity referred to as the receptor-associated prorenin system. Indeed, neovascular endothelial cells in the fibrovascular tissue collected from eyes with proliferative DR were immunoreactive for the receptor-associated prorenin system components including prorenin, (P)RR, phosphorylated extracellular signal-regulated kinase and VEGF-A. Protein levels of soluble (P)RR increased with its positive correlations with prorenin, renin enzymatic activity and VEGF in the vitreous of proliferative DR eyes, suggesting a close link between (P)RR and VEGF-A-driven angiogenic activity. Furthermore, we revealed an unsuspected, PAPS-independent role of (P)RR in glucose-induced oxidative stress. Recently, we developed an innovative single-strand ribonucleic acid interference molecule selectively targeting human and mouse (P)RR, and confirmed its efficacy in suppressing diabetes-induced retinal inflammation in mice. Our data using clinical samples and animal models suggested the significant implication of (P)RR in the pathogenesis of DR, and the potential usefulness of the ribonucleic acid interference molecule as a therapeutic agent to attenuate ocular inflammation and angiogenesis.

show abstract

“…We have previously reported positive relationships between serum levels of TG and s(P)RR in patients with EH [ 8 ] and in hemodialysis patients [ 9 ], suggesting the presence of interactions between lipid metabolism dysfunction and serum s(P)RR levels. Although the reason for these associations is unknown, one may consider that patients with high TG levels may have increased expression of (P)RR in the hypertrophied adipose tissue to cause an elevation in serum s(P)RR levels.…”

Section: Discussionmentioning

confidence: 99%

“…(P)RR, which consists of 350 amino acids with a single transmembrane domain, is cleaved by furin to generate soluble (s)(P)RR, which is secreted into the extracellular space and found in blood [ 6 ]. These findings suggest that s(P)RR can serve as a biomarker reflecting the tissue RAS status [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

et al. 2018

Self Cite

View full text Add to dashboard Cite

Antithyroid drugs are generally selected as the first-line treatment for Graves’ Disease (GD); however, the existence of patients showing resistance or severe side effects to these drugs is an important issue to be solved. The (pro)renin receptor [(P)RR] is a multi-functional protein that activates the tissue renin-angiotensin system and is an essential constituent of vacuolar H+-ATPase, necessary for the autophagy-lysosome pathway. (P)RR is cleaved to soluble (s)(P)RR, which reflects the status of (P)RR expression. In this retrospective study, we aimed to investigate whether serum s(P)RR concentration can be used as a biomarker to predict the outcome of antithyroid drug treatment in GD patients. Serum s(P)RR levels were measured in 54 untreated GD patients and 7 control participants. Effects of medical treatment with antithyroid drugs on these levels were investigated in GD patients. Serum s(P)RR levels were significantly higher in patients with Graves’ disease than in control subjects (P<0.005) and were significantly reduced after medical treatment for Graves’ disease. High serum s(P)RR levels were associated with resistance to antithyroid drug treatment, suggesting that serum s(P)RR concentration can be used as a useful biomarker to predict the outcome of antithyroid drug treatment in these patients. Patients with Graves’ disease with low body mass index showed higher levels of serum soluble (pro)renin receptor levels than those with high body mass index. In addition, in patients with Graves’ disease, serum triglyceride levels were negatively correlated with serum soluble (pro)renin receptor levels. All these data indicated an association between low nutrient condition due to hyperthyroidism and increased (pro)renin receptor expression in these patients, suggesting that (pro)renin receptor expression could be increased in the process of stimulating intracellular energy production via activating autophagy function to compensate energy loss.

show abstract

Serum Soluble (Pro)Renin Receptor Levels in Maintenance Hemodialysis Patients

Cited by 20 publications

References 38 publications

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy

Systemic factors related to soluble (pro)renin receptor in plasma of patients with proliferative diabetic retinopathy

(Pro)renin receptor: Involvement in diabetic retinopathy and development of molecular targeted therapy

Prediction of response to medical therapy by serum soluble (pro)renin receptor levels in Graves’ disease

Contact Info

Product

Resources

About