Related Experiment Video
Updated: Feb 26, 2026
Characterization of Neuromuscular Junctions in Mice by Combined Confocal and Super-Resolution Microscopy
Published on: December 8, 2021
Minnelide ameliorates Col4a5+/- mice by upregulating Col4a5 and alleviating endoplasmic reticulum stress
Bao-Wei Ji1,2,3, Jun-Chao Liu4, Xue Wang5
1Department of Nephrology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
Background:
Alport syndrome (AS) is a progressive hereditary nephropathy caused by mutations in collagen IV genes, notably COL4A5, leading to proteinuria and kidney failure. Current therapies using RAAS inhibitors show limited efficacy. Triptolide, the main active component of Tripterygium wilfordii, exhibits anti-proteinuric effects but is limited by poor solubility and toxicity. Minnelide, its water-soluble prodrug, provides a promising alternative.
Objective:
This study investigated the therapeutic potential and mechanisms of Minnelide in a female Col4a5 (X + X-) Alport syndrome mouse model.
Methods:
Mice were treated with Minnelide or vehicle for 3 months. In vitro, Col4a5+/- podocytes were treated with triptolide, with or without Col4a5 siRNA knockdown.
Results:
Minnelide significantly reduced proteinuria by 64.2%, improved glomerular pathology, upregulated renal Col4a5 expression, and suppressed endoplasmic reticulum (ER) stress. In podocytes, triptolide increased Col4a5 and alleviated ER stress. Col4a5 knockdown directly induced ER stress, which was reversed by triptolide treatment.
Conclusion:
Minnelide demonstrates potent renoprotective effects in AS by upregulating Col4a5 expression and mitigating podocyte ER stress, positioning it as a novel therapeutic candidate.
Insights
Minnelide effectively treats Alport syndrome by reducing proteinuria and improving kidney health. This novel drug upregulates collagen IV alpha 5 (COL4A5) expression and reduces endoplasmic reticulum stress in podocytes.
Area of Science:
- Nephrology
- Genetics
- Pharmacology
Background:
- Alport syndrome (AS) is a hereditary kidney disease caused by collagen IV gene mutations, leading to kidney failure.
- Current treatments for AS, like RAAS inhibitors, have limited effectiveness.
- Triptolide shows anti-proteinuric effects but has poor solubility and toxicity; Minnelide, a water-soluble prodrug, offers a promising alternative.
Purpose of the Study:
- To investigate the therapeutic potential and mechanisms of Minnelide in a mouse model of Alport syndrome.
- To evaluate Minnelide's effects on proteinuria, glomerular pathology, and underlying molecular pathways in AS.
Main Methods:
- Treatment of a female Col4a5 (X + X-) Alport syndrome mouse model with Minnelide or vehicle for three months.
- In vitro studies involving treatment of Col4a5+/- podocytes with triptolide, with or without Col4a5 siRNA knockdown.
Main Results:
- Minnelide significantly reduced proteinuria by 64.2% and improved glomerular pathology.
- Minnelide upregulated renal Col4a5 expression and suppressed endoplasmic reticulum (ER) stress.
- Triptolide increased Col4a5 expression and alleviated ER stress in podocytes, with Col4a5 knockdown directly inducing ER stress.
Conclusions:
- Minnelide exhibits potent renoprotective effects in Alport syndrome.
- The drug functions by upregulating Col4a5 expression and mitigating podocyte ER stress.
- Minnelide represents a novel therapeutic candidate for Alport syndrome treatment.
