Related Experiment Video
Updated: Aug 12, 2025
Mechanism of Kemeng Fang's Inhibition of Podocyte Apoptosis in Rats with Membranous Nephropathy through the PI3K/AKT Signaling Pathway
Published on: August 23, 2024
Endotrophin neutralization through targeted antibody treatment protects from renal fibrosis in a podocyte ablation
Yu A An1, Wei Xiong2, Shiuhwei Chen3
1Touchstone Diabetes Center, The University of Texas Southwestern Medical Center, Dallas, TX, USA; Department of Anesthesiology, Critical Care and Pain Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA.
Objective:
Renal fibrosis is a hallmark for chronic kidney disease (CKD), and often leads to end stage renal disease (ESRD). However, limited interventions are available clinically to ameliorate or reverse renal fibrosis.
Methods:
Herein, we evaluated whether blockade of endotrophin through neutralizing antibodies protects from renal fibrosis in the podocyte insult model (the "POD-ATTAC" mouse). We determined the therapeutic effects of endotrophin targeted antibody through assessing renal function, renal inflammation and fibrosis at histological and transcriptional levels, and podocyte regeneration.
Results:
We demonstrated that neutralizing endotrophin antibody treatment significantly ameliorates renal fibrosis at the transcriptional, morphological, and functional levels. In the antibody treatment group, expression of pro-inflammatory and pro-fibrotic genes was significantly reduced, normal renal structures were restored, collagen deposition was decreased, and proteinuria and renal function were improved. We further performed a lineage tracing study confirming that podocytes regenerate as de novo podocytes upon injury and loss, and blockade of endotrophin efficiently enhances podocyte-specific marker expressions.
Conclusion:
Combined, we provide pre-clinical evidence supporting neutralizing endotrophin as a promising therapy for intervening with renal fibrosis in CKD, and potentially in other chronic fibro-inflammatory diseases.
Insights
Neutralizing endotrophin with antibodies shows promise in treating kidney fibrosis. This approach improved kidney function and structure in preclinical models, offering hope for chronic kidney disease patients.
Area of Science:
- Nephrology
- Immunology
- Fibrosis Research
Background:
- Renal fibrosis is a critical factor in chronic kidney disease (CKD) progression, often leading to end-stage renal disease (ESRD).
- Current therapeutic options for reversing renal fibrosis are limited, highlighting the need for novel interventions.
Purpose of the Study:
- To investigate the therapeutic potential of blocking endotrophin using neutralizing antibodies.
- To evaluate the efficacy of endotrophin blockade in ameliorating renal fibrosis in a mouse model.
Main Methods:
- Utilized the POD-ATTAC mouse model with podocyte injury to induce renal fibrosis.
- Administered endotrophin-neutralizing antibodies and assessed therapeutic effects on renal function, inflammation, fibrosis, and podocyte regeneration.
- Analyzed histological, transcriptional, and functional parameters to determine treatment outcomes.
Main Results:
- Endotrophin antibody treatment significantly reduced renal fibrosis at transcriptional, morphological, and functional levels.
- Observed decreased expression of pro-inflammatory and pro-fibrotic genes, restoration of renal structures, and reduced collagen deposition.
- Demonstrated improved proteinuria and renal function, with enhanced podocyte regeneration and marker expression.
Conclusions:
- Pre-clinical data support endotrophin neutralization as a potential therapeutic strategy for renal fibrosis in CKD.
- This approach may also be beneficial for other chronic fibro-inflammatory diseases.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:29Acute Kidney Injury II: Pathophysiology
01:28Chronic Kidney Disease III: Interprofessional Care