Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

Zaade, Daniela; Schmitz, Jennifer; Benke, Eileen; Klare, Sabrina; Seidel, Kerstin; Kirsch, Sebastian; Goldin-Lang, Petra; Zollmann, Frank S.; Unger, Thomas; Funke-Kaiser, Heiko

doi:10.1371/journal.pone.0057674

Cited by 5 publications

(3 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although the function of TSTD2 has not yet been fully elucidated, its expression in the soleus feed artery can be upregulated by endurance exercise training ( 32 ). TSTD2 can function in the downstream region of the (pro)renin receptor signaling pathway ( 33 ). The renin-angiotensin system plays a key regulatory role in hypertension ( 34 ).…”

Section: Discussionmentioning

confidence: 99%

Serum anti‑TSTD2 antibody as a biomarker for atherosclerosis‑induced ischemic stroke and chronic kidney disease

Kubota

Zhang

et al. 2022

Med Int

View full text Add to dashboard Cite

autoantibodies can be used in the early diagnosis and treatment of atherosclerosis-related diseases. Using Protoarray ® screening of samples from patients with atherosclerosis, the present study identified thiosulfate sulfurtransferase-like domain-containing 2 (tStD2) as a novel atherosclerosis antigen. the serum tStD2 antibody levels were then quantified using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay. this demonstrated the levels of tStD2 antibodies (tStD2-abs) to be significantly higher in patients with acute cerebral infarction or chronic kidney disease than in healthy donors. the tStD2-ab levels were also found to be higher in males, older adults, smokers, in those who consumed alcohol regularly, and in those with hypertension. Furthermore, Spearman's rank correlation analysis revealed tStD2-ab levels to be strongly associated with measures of atherosclerosis severity, including plaque scores, intima-media thickness of the carotid artery and the cardio-ankle vascular index. thus, tStD2-abs may thus be a promising novel biomarker for atherosclerosis-related cerebral infarction and kidney disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum anti‑TSTD2 antibody as a biomarker for atherosclerosis‑induced ischemic stroke and chronic kidney disease

Kubota

Zhang

et al. 2022

Med Int

View full text Add to dashboard Cite

show abstract

“…Functional studies should also be performed to understand the basic role of PRR in bladder cancer biology and how this novel marker influences cancer progression and aggressiveness in UC. According to investigation performed in other tumor models, likely mechanisms are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function [ 39 ]. The role of PRR in cancer development and progression can also be supported by big data analysis from The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) data-bases in several malignancies [ 13 ], although further specific investigation is needed in UC.…”

Section: Discussionmentioning

confidence: 99%

(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder

Larrinaga

Calvete-Candenas

Solano-Iturri

et al. 2021

Cancers

View full text Add to dashboard Cite

(Pro)renin receptor (PRR) is being investigated in several malignancies as it activates pathogenic pathways that contribute to cell proliferation, immunosuppressive microenvironments, and acquisition of aggressive neoplastic phenotypes. Its implication in urothelial cancer (UC) has not been evaluated so far. We retrospectively evaluate the prognostic role of PRR expression in a series of patients with invasive UC treated with radical cystectomy and other clinical and histopathological parameters including p53, markers of immune-checkpoint inhibition, and basal and luminal phenotypes evaluated by tissue microarray. Cox regression analyses using stepwise selection evaluated candidate prognostic factors and disease-specific survival. PRR was expressed in 77.3% of the primary tumors and in 70% of positive lymph nodes. PRR expression correlated with age (p = 0.006) and was associated with lower preoperatively hemoglobin levels. No other statistical association was evidenced with clinical and pathological variables (gender, ASA score, Charlson comorbidity index, grade, pT, pN) or immunohistochemical expressions evaluated (CK20, GA-TA3, CK5/6, CD44, PD-L1, PD-1, B7-H3, VISTA, and p53). PRR expression in primary tumors was associated with worse survival (log-rank, p = 0.008). Cox regression revealed that PRR expression (HR 1.85, 95% CI 1.22–2.8), pT (HR 7.02, 95% CI 2.68–18.39), pN (HR 2.3, 95% CI 1.27–4.19), and p53 expression (HR 1.95, 95% CI 1.1–3.45) were independent prognostic factors in this series. In conclusion, we describe PRR protein and its prognostic role in invasive UC for the first time. Likely mechanisms involved are MAPK/ERK activation, Wnt/β-catenin signaling, and v-ATPAse function.

show abstract

“…The resulting acidic environment is crucial for many biological processes, such as intracellular trafficking and coupled transport of small molecules 13 14 . PRR also interacts with other signaling proteins independently from AngII generation, such as Wnt receptors 15 16 17 and the transcription factor promyelocytic leukemia zinc finger (PLZF) 18 19 20 . PLZF, originally identified as the fusion partner of the retinoic acid receptor α 21 , undergoes nuclear translocation following renin stimulation and represses transcription of PRR itself, as well as activates PI3K-p85α 18 .…”

mentioning

confidence: 99%

Regulation of growth hormone secretion by (pro)renin receptor

Tani

Yamada

Inoshita

et al. 2015

Sci Rep

View full text Add to dashboard Cite

(Pro)renin receptor (PRR) has a single transmembrane domain that co-purifies with the vacuolar H+-ATPase (V-ATPase). In addition to its role in cellular acidification, V-ATPase has been implicated in membrane fusion and exocytosis via its Vo domain. Results from the present study show that PRR is expressed in pituitary adenoma cells and regulates growth hormone (GH) release via V-ATPase-induced cellular acidification. Positive PRR immunoreactivity was detected more often in surgically resected, growth hormone-producing adenomas (GHomas) than in nonfunctional pituitary adenomas. GHomas strongly expressing PRR showed excess GH secretion, as evidenced by distinctly high plasma GH and insulin-like growth factor-1 levels, as well as an elevated nadir GH in response to the oral glucose tolerance test. Suppression of PRR expression in rat GHoma-derived GH3 cells using PRR siRNA resulted in reduced GH secretion and significantly enhanced intracellular GH accumulation. GH3 treatment with bafilomycin A1, a V-ATPase inhibitor, also blocked GH release, indicating mediation via impaired cellular acidification of V-ATPase. PRR knockdown decreased Atp6l, a subunit of the Vo domain that destabilizes V-ATPase assembly, increased intracellular GH, and decreased GH release. To our knowledge, this is the first report demonstrating a pivotal role for PRR in a pituitary hormone release mechanism.

show abstract

Distinct Signal Transduction Pathways Downstream of the (P)RR Revealed by Microarray and ChIP-chip Analyses

Cited by 5 publications

References 69 publications

Serum anti‑TSTD2 antibody as a biomarker for atherosclerosis‑induced ischemic stroke and chronic kidney disease

Serum anti‑TSTD2 antibody as a biomarker for atherosclerosis‑induced ischemic stroke and chronic kidney disease

(Pro)renin Receptor Is a Novel Independent Prognostic Marker in Invasive Urothelial Carcinoma of the Bladder

Regulation of growth hormone secretion by (pro)renin receptor

Contact Info

Product

Resources

About