The (pro)renin receptor and body fluid homeostasis

Cao, Theresa; Feng, Yi

doi:10.1152/ajpregu.00209.2013

Cited by 14 publications

(9 citation statements)

References 17 publications

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“…PRR is shown to be colocalized to the paraventricular and supraoptic nuclei of human hypothalamic with AVP 42 and functionally regulate central AVP production. 17,43,44 As expected, AVP level was unaffected by intrarenal PRR inhibition or CD PRR deficiency.…”

Section: Discussionsupporting

confidence: 76%

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4

Wang

Peng

et al. 2016

JASN

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Within the kidney, the (pro)renin receptor (PRR) is predominantly expressed in the collecting duct (CD), particularly in intercalated cells, and it is regulated by the PGE receptor EP Notably, EP also controls urinary concentration through regulation of aquaporin 2 (AQP2). Here, we tested the hypothesis that sequential activation of EP and PRR determines AQP2 expression in the CD, thus mediating the antidiuretic action of vasopressin (AVP). Water deprivation (WD) elevated renal PRR expression and urinary soluble PRR excretion in rats. Intrarenal infusion of a PRR decoy peptide, PRO20, or an EP antagonist partially prevented the decrease in urine volume and the increase in urine osmolality and AQP2 expression induced by 48-hour WD. In primary cultures of rat inner medullary CD cells, AQP2 expression induced by AVP treatment for 24 hours depended on sequential activation of the EP receptor and PRR. Additionally, mice lacking PRR in the CD exhibited increased urine volume and decreased urine osmolality under basal conditions and impaired urine concentrating capability accompanied by severe volume loss and a dangerous level of plasma hyperosmolality after WD. Together, these results suggest a previously undescribed linear AVP/PGE/EP/PRR pathway in the CD for regulation of AQP2 expression and urine concentrating capability.

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Section: Discussionsupporting

confidence: 76%

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4

Wang

Peng

et al. 2016

JASN

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“…Pro‐renin, a critical chaperone for the assembly of H + ‐ATPase subunits, regulates cell proliferation via the mitogen activated protein kinases ERK1/2 cascade and is a crucial component of Wnt pathways (Kaneshiro et al. ; Cao and Feng ; Seva Pessoa et al. ; Sihn et al.…”

Section: Resultsmentioning

confidence: 99%

“…We were intrigued by the H + -ATPase in the intercalated cells because in the kidney, the prorenin receptor (PRR) co-localizes with H + -ATPase in intercalated cells and functions as a receptor for renin. Pro-renin, a critical chaperone for the assembly of H + -ATPase subunits, regulates cell proliferation via the mitogen activated protein kinases ERK1/2 cascade and is a crucial component of Wnt pathways (Kaneshiro et al 2006;Cao and Feng 2013;Seva Pessoa et al 2013;Sihn et al 2013;Danser 2015;Ramkumar and Kohan 2016a,b;Peters 2017). There is robust and uniform PRR expression on the apical membrane of cyst epithelium in 11 weeks old Aqp2-CreTsc2 mice (Fig.…”

Section: Cellular Composition Of Tsc Cystic Epitheliummentioning

confidence: 98%

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

et al. 2019

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Tuberous sclerosis complex (TSC) is a tumor predisposition syndrome with significant renal cystic and solid tumor disease. While the most common renal tumor in TSC, the angiomyolipoma, exhibits a loss of heterozygosity associated with disease, we have discovered that the renal cystic epithelium is composed of type A intercalated cells that have an intact Tsc gene that have been induced to exhibit Tsc‐mutant disease phenotype. This mechanism appears to be different than that for ADPKD. The murine models described here closely resemble the human disease and both appear to be mTORC1 inhibitor responsive. The induction signaling driving cystogenesis may be mediated by extracellular vesicle trafficking.

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“…The renin-angiotensin system (RAS), as a major mechanism contributing to the regulation of blood pressure, body fluid, and tissue remodeling, has a critical role in the maintenance of tissue perfusion and homeostasis [1–3]. Seminal studies demonstrating the existence of an inhibitory arm of the RAS through the expression of angiotensin-(1-7) and angiotensin converting enzyme 2 (ACE2) [4] are now expanded with the discovery of an extended form of angiotensin I (Ang I) [5] which our laboratory characterized as an intracrine tissue precursor for direct angiotensin II (Ang II) production [6–8].…”

Section: Introductionmentioning

confidence: 99%

Primacy of cardiac chymase over angiotensin converting enzyme as an angiotensin-(1-12) metabolizing enzyme

Ahmad

Varagić

VonCannon

et al. 2016

Biochemical and Biophysical Research Communications

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We showed previously that rat angiotensin-(1-12) [Ang-(1-12)] is metabolized by chymase and angiotensin converting enzyme (ACE) to generate Angiotensin II (Ang II). Here, we investigated the affinity of cardiac chymase and ACE enzymes for Ang-(1-12) and Angiotensin I (Ang I) substrates. Native plasma membranes (PMs) isolated from heart and lung tissues of adult spontaneously hypertensive rats (SHR) were incubated with radiolabeled 125I-Ang-(1-12) or 125I-Ang I, in the absence or presence of a chymase or ACE inhibitor (chymostatin and lisinopril, respectively). Products were quantitated by HPLC connected to an in-line flow-through gamma detector. The rate of 125I-Ang II formation from 125I-Ang-(1-12) by chymase was significantly higher (heart: 7.0 ± 0.6 fmol/min/mg; lung: 33 ± 1.2 fmol/min/mg, P < 0.001) when compared to 125I-Ang I substrate (heart: 0.8 ± 0.1 fmol/min/mg; lung: 2.1 ± 0.1 fmol/min/mg). Substrate affinity of 125I-Ang-(1-12) for rat cardiac chymase was also confirmed using excess unlabeled Ang-(1-12) or Ang I (0–250 µM). The rate of 125I-Ang II formation was significantly lower using unlabeled Ang-(1-12) compared to unlabeled Ang I substrate. Kinetic data showed that rat chymase has a lower Km (64 ± 6.3 µM vs 142 ± 17 µM), higher Vmax (13.2 ± 1.3 µM/min/mg vs 1.9 ± 0.2 µM/min/mg) and more than 15-fold higher catalytic efficiency (ratio of Vmax/Km) for Ang-(1-12) compared to Ang I substrate, respectively. We also investigated ACE mediated hydrolysis of 125I-Ang-(1-12) and 125I-Ang I in solubilized membrane fractions of the SHR heart and lung. Interestingly, no significant difference in 125I-Ang II formation by ACE was detected using either substrate, 125I-Ang-(1-12) or 125I-Ang I, both in the heart (1.8 ± 0.2 fmol/min/mg and 1.8 ± 0.3 fmol/min/mg, respectively) and in the lungs (239 ± 25 fmol/min/mg and 248 ± 34 fmol/min/mg, respectively). Compared to chymase, ACE-mediated Ang-(1-12) metabolism in the heart was several fold lower. Overall our findings suggest that Ang-(1-12), not Ang I, is the better substrate for Ang II formation by chymase in adult rats. In addition, this confirms our previous observation that chymase (rather than ACE) is the main hydrolyzing enzyme responsible for Ang II generation from Ang-(1-12) in the adult rat heart.

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The (pro)renin receptor and body fluid homeostasis

Cited by 14 publications

References 17 publications

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4

Antidiuretic Action of Collecting Duct (Pro)Renin Receptor Downstream of Vasopressin and PGE2 Receptor EP4

Tuberous sclerosis complex exhibits a new renal cystogenic mechanism

Primacy of cardiac chymase over angiotensin converting enzyme as an angiotensin-(1-12) metabolizing enzyme

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