Related Experiment Video

Updated: Aug 18, 2025

5/6 Nephrectomy Using Sharp Bipolectomy Via Midline Laparotomy in Rats
05:34

5/6 Nephrectomy Using Sharp Bipolectomy Via Midline Laparotomy in Rats

Published on: April 4, 2025

766

Targeting endogenous kidney regeneration using anti-IL11 therapy in acute and chronic models of kidney disease

Anissa A Widjaja1, Sivakumar Viswanathan2, Shamini G Shekeran2

  • 1Cardiovascular and Metabolic Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. anissa.widjaja@duke-nus.edu.sg.

Nature Communications
|December 5, 2022
PubMed

Insights

Interleukin-11 (IL11) drives kidney dysfunction and hinders repair by causing renal tubular epithelial cells (TECs) to arrest growth. Blocking IL11 promotes kidney regeneration and restores function in disease models.

Area of Science:

  • Nephrology
  • Cell Biology
  • Immunology

Background:

  • Kidney damage often impairs the organ's regenerative capacity.
  • Renal tubular epithelial cells (TECs) can enter SNAI1-driven growth arrest, hindering repair.
  • The role of Interleukin-11 (IL11) in TECs during kidney injury and repair requires further investigation.

Purpose of the Study:

  • To investigate the role of IL11 in TECs during kidney injury and repair.
  • To determine if IL11 blockade can restore kidney function and regeneration.

Main Methods:

  • Studied IL11 stimulation effects on TECs, including signaling pathways and gene expression.
  • Utilized mouse models of acute kidney injury (AKI) and chronic kidney disease (CKD).
  • Employed IL11 knockout mice, IL11 neutralizing antibodies, and TEC-specific Il11ra1 deletion models.

Main Results:

  • IL11 stimulation of TECs induced GSK3β inactivation, SNAI1 upregulation, and inflammation.
  • IL11 upregulation in AKI correlated with kidney dysfunction, which was prevented by IL11 deletion or blockade.
  • Anti-IL11 therapy, unlike anti-TGFβ, reduced inflammation, fibrosis, and tubule damage in AKI.
  • TEC-specific Il11ra1 deletion protected against AKI-induced pathologies.
  • Anti-IL11 treatment in CKD models promoted TEC proliferation, regeneration, and restored renal function.

Conclusions:

  • IL11 drives TECs towards a pathogenic mesenchymal transition, impairing kidney regeneration.
  • IL11 blockade represents a promising therapeutic strategy for promoting kidney repair and treating kidney disease.

More Related Videos

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration12:27

Renal Ischaemia Reperfusion Injury: A Mouse Model of Injury and Regeneration

Published on: June 7, 2014

50.0K
A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion09:02

A Large Animal Model for Acute Kidney Injury by Temporary Bilateral Renal Artery Occlusion

Published on: February 2, 2021

4.5K

Related Concept Videos

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...
53
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...
49
Chronic Kidney Disease III: Interprofessional Care01:28

Chronic Kidney Disease III: Interprofessional Care

Chronic kidney disease (CKD) requires collaborative and comprehensive management. CKD progresses through stages and can lead to end-stage kidney disease (ESKD) if untreated. Interprofessional collaboration and patient education are crucial, enabling patients to manage their health and improve their quality of life.Diagnostic approach for chronic kidney diseaseThe diagnosis of CKD primarily focuses on the glomerular filtration rate (GFR), which assesses kidney function by measuring how well...
68
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...
58
Acute Kidney Injury V: Interprofessional Care01:20

Acute Kidney Injury V: Interprofessional Care

Acute Kidney Injury (AKI) requires a collaborative healthcare approach to restore renal function and prevent complications. Essential management strategies involve monitoring fluid and electrolyte balance, adjusting medications, initiating dialysis when necessary, and providing nutritional support.Fluid and Electrolyte ManagementFluid Monitoring: Regularly monitoring body weight, central venous pressure, and urine output helps detect fluid imbalances early. Patient intake and output are...
40
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...
54