Related Experiment Video

Updated: May 20, 2026

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection
10:15

Identification of the Source of Secreted Proteins in the Kidney by Brefeldin A Injection

Published on: November 10, 2021

4-1BB-mediated signals confer protection against folic acid-induced nephrotoxicity

Xiaozhong Li1, Jihong Dai, Yuhua Qiu

  • 1Children Hospital & Medical Bio-tech Institute Affiliated to Soochow University, #303 Jingde Road, Suzhou Jiangsu 215003, China. xiaozhonglicn@yeah.net

Kidney & Blood Pressure Research
|July 11, 2012
PubMed
Abstract

Insights

Targeting 4-1BB (a co-stimulatory molecule) in folic acid-induced nephrotoxicity reduced kidney damage and improved renal function. This approach attenuated early immune pathology and reversed later-stage immune suppression in mice.

Area of Science:

  • Nephrology
  • Immunology
  • Molecular Biology

Background:

  • The role of co-stimulatory molecules in renal diseases is not fully understood, particularly 4-1BB in nonimmune-mediated tubulointerstitial fibrosis.
  • Folic acid-induced nephrotoxicity (FAN) in mice serves as a model to investigate 4-1BB's function in renal disease.

Purpose of the Study:

  • To explore the role of the co-stimulatory molecule 4-1BB in folic acid-induced nephrotoxicity.
  • To evaluate the therapeutic potential of targeting 4-1BB in a mouse model of renal tubulointerstitial fibrosis.

Main Methods:

  • CD1 mice were administered folic acid to induce nephrotoxicity.
  • Kidneys were analyzed using histochemistry, T cell profiling, and renal function tests.
  • Mice were co-treated with agonistic anti-4-1BB monoclonal antibodies.

Main Results:

  • Co-treatment with anti-4-1BB antibodies reduced renal tubulointerstitial lesions and improved renal function (decreased BUN and sCr levels).
  • 4-1BB treatment modulated T cell profiles, attenuating early-stage immunopathology and reversing late-stage immunosuppression.
  • Histochemistry revealed reduced kidney damage in 4-1BB treated mice.

Conclusions:

  • 4-1BB signaling exerts immunoregulatory effects in the context of folic acid-induced nephrotoxicity.
  • Targeting 4-1BB can attenuate early immune-mediated pathology and reverse the immunocompromised state in later disease stages.
  • These findings suggest 4-1BB as a potential therapeutic target for nonimmune-mediated renal tubulointerstitial fibrosis.

More Related Videos

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform06:21

Multi-Gene Single Nucleotide Polymorphism Detection in Gastric Cancer Based on Ion Semiconductor Sequencing Platform

Published on: May 10, 2024

Related Concept Videos

Combined Effects of Drugs: Synergism01:27

Combined Effects of Drugs: Synergism

Synergism is a useful mechanism where combining two or more drugs is more effective than each constituent used alone. Such combinations are also called supra-additive interactions. The drugs collectively enhance the final therapeutic effect by acting on different targets. Another advantage is that the low dose of each constituent drug is sufficient to achieve the desired effect. This helps reduce the duration of therapy and lower the adverse effects of these drugs.
Such synergistic combinations...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
Antifungal Agents01:15

Antifungal Agents

Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to cholesterol contributes to...
Biosynthesis of Nucleic Acids01:28

Biosynthesis of Nucleic Acids

Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase01:27

Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase

Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
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...