Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism

Recarti, Chiara; Seccia, Teresa Maria; Caroccia, Brasilina; Gonzales-Campos, Abril; Ceolotto, Giulio; Lenzini, Livia; Petrelli, Lucía; Belloni, Anna S.; Rainey, William E.; Nussberger, Juerg

doi:10.1097/hjh.0000000000000504

Cited by 9 publications

(5 citation statements)

References 32 publications

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“…Our data show cytoplasmic granular staining of PRR in RCCs, which could be associated with these intracellular phenomena. PRR has also been described in benign tumours, such as adrenal [46,47] and colorectal adenomas [27]. In agreement with this, our results showed that PRR was expressed in RO and with the same intensity as in ChRCC, tumours that are histogenetically related [6].…”

Section: Discussionsupporting

confidence: 91%

Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours

et al. 2021

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(1) Background: Renal cancer is one of the most frequent malignancies in Western countries, with an unpredictable clinical outcome, partly due to its high heterogeneity and the scarcity of reliable biomarkers of tumour progression. (Pro)renin receptor (PRR) is a novel receptor of the renin–angiotensin system (RAS) that has been associated with the development and progression of some solid tumours by RAS-dependent and -independent mechanisms. (2) Methods: In this study, we analysed the immunohistochemical expression of PRR at the centre and border in a series of 83 clear-cell renal cell (CCRCCs), 19 papillary (PRCC) and 7 chromophobe (ChRCC) renal cell carcinomas, and the benign tumour renal oncocytoma (RO, n = 11). (3) Results: PRR is expressed in all the tumour subtypes, with higher mean staining intensity in ChRCCs and ROs. A high expression of PRR at the tumour centre and at the infiltrative front of CCRCC tissues is significantly associated with high grade, tumour diameter, local invasion and stage, and with high mortality risk by UCLA integrated staging system (UISS) scale. (4) Conclusions: These findings indicate that PRR is associated with the development and progression of renal tumours. Its potential as a novel biomarker for RCC diagnosis/prognosis and as a promising therapeutic target should be taken into account in the future.

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Section: Discussionsupporting

confidence: 91%

Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours

et al. 2021

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Section: Aldosterone-producing Adenoma (Apa)mentioning

confidence: 99%

“…Recarti et al [46] have detected high expression of (P) RR in APA tissues and HAC15 adrenocortical carcinoma cells that can produce aldosterone once treated with Ang II. Binding of prorenin and (P) RR could trigger the expression of the aldosterone synthase CYP11B2 and ERK1/2 phosphorylation, thus promoting the production and secretion of aldosterone [46]. Furthermore, Yamamoto et al [15] revealed that both the mRNA and protein expression levels of (P) RR are elevated in tumor tissues of APAs relative to these levels in the matched non-neoplastic adrenal tissues and tissues from (See figure on previous page.)…”

Section: Aldosterone-producing Adenoma (Apa)mentioning

confidence: 99%

The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers

et al. 2020

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Background: The (pro) renin receptor ((P)RR) plays important roles in various pathways, such as the Wnt/β-catenin, renin-angiotensin system (RAS), MAPK/ERK and PI3K/AKT/mTOR pathways, that are involved in a wide range of physiological and pathological processes incorporating the tumorigenesis. However, our knowledge about (P) RR was mostly limited to its roles in cardiovascular and renal physiological functions and diseases. In the past 5 years, however, compelling evidence has revealed that (P) RR is aberrantly expressed in and contributes to the development of various cancers by different means. For instance, (P) RR was recently demonstrated to induce the oncogenesis of pancreatic, colorectal and brain cancers via the Wnt signaling, while promote the endometrial cancer and glioblastoma through the RAS. Methods: Combining with the deep analysis of big data from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases, this review updates and summarizes the recent studies about the newly recognized roles of (P) RR in the pathophysiological processes of cancer development and its detailed functions through related pathways, as well as the novel research progress of (P) RR in related fields including the development and application of soluble (P) RR detection kit and monoclonal (P) RR antibody. Results: This review provides an overview of the essential roles of (P) RR in the tumorigenesis and progression of various cancers and offers a translational outlook for the future research and clinical practices. Conclusion: (P) RR in the tumor tissues and/or body fluids of patients may be a novel and promising biomarker and potential therapeutic target for diagnosis, treatment and prognosis prediction in various cancers.

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“…These findings may therefore indicate that (P)RR plays a crucial role in the CYP11B2 transcription through activation of the Wnt/ β -catenin signaling pathway. On the other hand, a previous in vitro study using HAC15 adrenocortical cells demonstrated that the binding of prorenin to (P)RR triggers the generation of angiotensin I from angiotensinogen, ensuring the formation of angiotensin II and activation of the AT1R leading to transcription of CYP11B2 and amplification of aldosterone production [ 24 ]. These findings and our immunohistochemical staining results raised the possibility that (P)RR plays an important role in the regulation and/or production of aldosterone through activation of CYP11B2 transcription in human APA tissues.…”

Section: Discussionmentioning

confidence: 99%

Adrenal (Pro)renin Receptor Expression and Serum Soluble (Pro)renin Receptor Concentration in Primary Aldosteronism

Watanabe

Morimoto

Morishima

et al. 2020

International Journal of Endocrinology

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The (pro)renin receptor [(P)RR] is a multifunctioning protein playing roles in various pathological conditions. A soluble form of (P)RR [s(P)RR] has been considered a biomarker for (P)RR expression in tissues. Expression of (P)RR has been described in aldosterone-producing adenoma (APA), but the roles of (P)RR have yet to be fully determined. This study investigated the significance of (P)RR and serum s(P)RR concentrations in patients with APA. We evaluated associations between (P)RR expression and expression of CYP11B2, an aldosterone synthase, and aldosterone production by the adrenal glands and assessed the relationships between serum s(P)RR concentration and background factors. (P)RR colocalized with CYP11B2 and expression levels of (P)RR were positively associated with those of CYP11B2 in APA tissues. (P)RR immunoreactivity in these tissues correlated positively with plasma aldosterone concentrations (PAC) and urinary aldosterone excretion. Also, in APA, (P)RR mRNA abundance was positively correlated with β-catenin mRNA abundance. Significant positive correlations were identified between serum s(P)RR concentration and plasma glucose, hemoglobin A1c, and serum creatinine levels, but not with PAC (in either peripheral vein or adrenal vein) or adrenal (P)RR expression level. This study showed that (P)RR expression level correlates with CYP11B2 expression in APA tissues and PAC and urinary aldosterone excretion, suggesting that (P)RR expression may contribute to aldosterone synthesis via CYP11B2 activation in APAs, although serum s(P)RR concentration failed to show any significant relationship with adrenal (P)RR expression. Adrenal (P)RR activity might offer a therapeutic target in the treatment of PA, although this issue needs to be investigated in future studies.

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Expression and functional role of the prorenin receptor in the human adrenocortical zona glomerulosa and in primary aldosteronism

Cited by 9 publications

References 32 publications

Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours

Clinical Implications of (Pro)renin Receptor (PRR) Expression in Renal Tumours

The (pro)renin receptor: a novel biomarker and potential therapeutic target for various cancers

Adrenal (Pro)renin Receptor Expression and Serum Soluble (Pro)renin Receptor Concentration in Primary Aldosteronism

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