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Related Concept Videos

Acute Kidney Injury II: Pathophysiology01:29

Acute Kidney Injury II: Pathophysiology

Acute kidney injury (AKI) causes are categorized into three primary categories based on the location of the injury: prerenal, intrarenal (or intrinsic), and postrenal causes. This classification guides clinical management and illustrates how different pathways can impair kidney function.Etiology and Pathophysiology of Acute Kidney Injury1. Prerenal causesEtiology: Prerenal Acute Kidney Injury, the most common type, occurs when reduced blood flow to the kidneys decreases filtration capacity...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Notch Signaling Pathway03:14

Notch Signaling Pathway

The Notch signaling pathway is a major intracellular signaling pathway that is highly conserved over a broad spectrum of metazoan species. It stands unique from other intracellular signaling mechanisms in animals because notch protein itself acts as the receptor as well as the primary signaling molecule.
The Notch gene came into the limelight in 1914 after the discovery that its mutation in Drosophila melanogaster leads to a serrated (or "notched") wing margin phenotype. It was not until 1985...
Acute Kidney Injury III: Clinical Manifestations01:29

Acute Kidney Injury III: Clinical Manifestations

Acute Kidney Injury (AKI) progresses through distinct clinical phases: the oliguric, diuretic, and recovery phases, each marked by unique manifestations and challenges.Oliguric Phase:The oliguric phase is the initial stage of AKI, typically lasting 10 to 14 days. This phase is marked by a significant reduction in urine output, usually less than 400 mL per day, indicating decreased kidney function. Fluid retention is a prominent feature, leading to symptoms such as edema, hypertension, and...
Acute Kidney Injury IV: Diagnostic Studies and Prevention01:30

Acute Kidney Injury IV: Diagnostic Studies and Prevention

Accurate diagnosis and effective prevention are critical in managing Acute Kidney Injury (AKI), which is linked to high mortality rates ranging from 10% to 80%. Timely recognition of at-risk patients and careful monitoring can significantly reduce the likelihood of kidney damage.Diagnostic Assessments:The diagnostic process starts with a comprehensive medical history to identify prerenal, intrarenal, and postrenal causes.Prerenal causes, such as dehydration, hypotension, or blood loss, should...
Acute Kidney Injury I: Introduction01:22

Acute Kidney Injury I: Introduction

Introduction:Acute Kidney Injury (AKI) describes a swift decrease in kidney function occurring over hours to days, characterized by the kidneys' failure to remove waste products from the bloodstream. This leads to dangerous complications like metabolic acidosis, fluid overload, and electrolyte imbalances, such as hyperkalemia, which can cause life-threatening arrhythmias. AKI is common in both hospital and outpatient settings, often triggered by dehydration, sepsis, or exposure to nephrotoxic...

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Related Experiment Video

Updated: May 18, 2026

Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes
11:47

Using 2-Photon Microscopy to Quantify the Effects of Chronic Unilateral Ureteral Obstruction on Glomerular Processes

Published on: March 4, 2022

Notch3 and kidney injury: never two without three.

Maria Dolores Sanchez-Niño1, Alberto Ortiz

  • 1Servicio de Nefrologia, IdiPAZ, Madrid, 28046, Spain.

The Journal of Pathology
|September 7, 2012
PubMed
Summary

The Notch signaling pathway plays a significant role in kidney injury, with specific receptors contributing to disease progression. Targeting individual Notch receptors offers potential for novel therapeutic strategies in kidney disease.

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Area of Science:

  • Nephrology
  • Molecular Biology
  • Cell Signaling

Background:

  • The Notch pathway, involving transmembrane receptors and ligands, regulates cell-cell communication.
  • Activation of Notch signaling and its downstream targets is implicated in the pathogenesis of kidney injury.
  • Current therapeutic strategies targeting the Notch pathway, such as γ-secretase inhibitors, show promise but have limitations due to off-target effects and toxicity.

Purpose of the Study:

  • To investigate the specific roles of individual Notch receptors (Notch1, Notch2, Notch3, Notch4) in kidney injury.
  • To explore the potential of targeted therapies by understanding the distinct contributions of each receptor.
  • To evaluate the therapeutic potential of blocking antibodies against specific Notch receptors.

Main Methods:

  • Analysis of Notch pathway activation in kidney injury models.
  • Overexpression studies of Notch intracellular domains (NICD1-4) in renal cells.
  • Immunostaining for NICD1, NICD2, and NICD4 in human and experimental kidney disease.
  • Genetic manipulation (conditional inactivation) of Notch1 and Notch2.
  • Phenotypic analysis of Notch3 knockout mice under different injury models.

Main Results:

  • Overexpression of NICD1-4 elicits distinct cellular responses including proliferation, apoptosis, inflammation, and fibrosis in renal cells.
  • Evidence of Notch receptor activation observed in glomerular and tubular cells in kidney disease.
  • Notch1/Notch2 inactivation influences cyst formation; NICD1 overexpression promotes glomerulosclerosis and fibrosis.
  • Notch2 mutations are linked to kidney injury in humans; Notch3 mutations are associated with renal injury in CADASIL.
  • Notch3 knockout mice exhibit differential sensitivity to specific kidney injury types.

Conclusions:

  • Specific Notch receptors play distinct roles in the development and progression of kidney injury.
  • Targeting individual Notch receptors, potentially using blocking antibodies, represents a promising therapeutic avenue for kidney diseases.
  • Further research is needed to fully elucidate the complex contributions of each Notch receptor to renal pathophysiology.