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June 1, 2002Journal of Clinical InvestigationOpen Access

Pivotal role of the renin/prorenin receptor in angiotensin II production and cellular responses to renin

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Key result

The binding of renin to its newly cloned receptor induced a fourfold increase in the catalytic efficiency of angiotensinogen conversion to angiotensin I and activated MAP kinases ERK1 and ERK2.

Population

Human kidney cDNA-phage library, human fetal mesangial cell line, and human tissue biopsies

Comparison

Expression cloning of the human renin receptor… vs Control cells transfected with empty vector…

Design

Preclinical

Authors

GNGeneviève NguyenInstitut National Polytechnique de ToulouseFDF DelarueInsermCBCéline BurckléCentre National de la Recherche Scientifique

Discussion

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Implication

Renin receptor discovery leaves open novel RAS modulation strategies; hypothesis-generating in animal models pending human validation.

Key Points

  • The research investigates the role of the renin receptor in angiotensin II production and cellular responses to renin.
  • Expression cloning of human renin receptor complementary DNA encoding a 350-amino acid protein.
  • Transfected cells were analyzed for renin- and prorenin-specific binding and catalytic efficiency.
  • Localization studies utilized confocal microscopy to observe receptor expression in various tissues.
  • Binding of renin increased the catalytic efficiency of angiotensinogen conversion to angiotensin I by fourfold.
  • Intracellular signaling was indicated by phosphorylation of serine and tyrosine residues and activation of MAP kinases ERK1 and ERK2.
  • High levels of renin receptor mRNA were found in heart, brain, and placenta, with lower levels in kidney and liver.

Structured PICO

P
Population
Human kidney cDNA-phage library, human fetal mesangial cell line (HMC), and human tissue biopsies (kidney, heart, placenta)
I
Intervention
Expression cloning of the human renin receptor (N14F) and stimulation with recombinant human renin and prorenin
C
Comparator
Control cells transfected with empty vector; soluble renin compared to membrane-bound renin
O
Outcome
Identification of the renin receptor, binding kinetics (Kd, Bmax), catalytic efficiency of angiotensinogen cleavage, and intracellular signaling activation (MAP kinases ERK1/ERK2)surrogate

The discovery of the renin receptor demonstrates that renin binding to cell surfaces increases angiotensin II generation and triggers intracellular signaling independent of angiotensin II.

Cite This Study

Nguyen et al. (2002) studied this question. Renin receptor cloning and characterization was evaluated on Catalytic efficiency of angiotensinogen conversion and intracellular signaling. The binding of renin to its newly cloned receptor induced a fourfold increase in the catalytic efficiency of angiotensinogen conversion to angiotensin I and activated MAP kinases ERK1 and ERK2.

synapsesocial.com/papers/6a2017e6a05ff06c2ba1a3fehttps://doi.org/10.1172/jci14276
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Identification of vascular renin-binding proteins by chemical cross-linking1994 · 44 citations
  2. 2Mannose 6-Phosphate Receptor–Mediated Internalization and Activation of Prorenin by Cardiac Cells1997 · 143 citations
  3. 3Divergent functions of angiotensin II receptor isoforms in the brain2000 · 202 citations
  4. 4An intact renin – angiotensin system is a prerequisite for normal renal development2000 · 225 citations
  5. 5Vascular damage without hypertension in transgenic rats expressing prorenin exclusively in the liver.1996 · 175 citations