Abstract: TH-PO0375
BMPR2 Deficiency Aggravates Podocyte Injury via Aberrant TGF-β/DACH1 Signaling in Diabetic Kidney Disease
Session Information
- Glomerular Diseases: Genetics to Therapeutics
October 22, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1401 Glomerular Diseases: Mechanisms, including Podocyte Biology
Authors
- Tang, Sixian, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Chen, Ying, Shanghai PuTuo District Center Hospital, Shanghai, China
- Jiang, Jiawang, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Wang, Niansong, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- He, Li, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Fei, Yang, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Cao, Aili, Department of Nephrology, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
Background
The clinical management of diabetic kidney disease (DKD) remains unsolved because podocyte damage functions as the primary disease mechanism. The downregulation of Bone morphogenetic protein receptor 2 (BMPR2) in podocyte cells during DKD makes it an attractive therapeutic target.
Methods
Here, we used human kidney transcriptome data to verify that DKD patients show decreased BMPR2 expression which directly relates to estimated glomerular filtration rate. The expression of BMPR2 in cultured podocytes decreased when cells were exposed to high glucose conditions or palmitic acid treatment. The RNA sequencing results from BMPR2-deficient podocytes showed strong activation of TGF-β signaling pathway.
Results
The absence of BMPR2 function made cells more susceptible to TGF-β-induced damage which resulted in decreased cell survival and movement and disrupted cytoskeletal structure through reduced synapotopodin and β-catenin expression. The initial exposure to TGF-β caused Dachshund homolog 1 (DACH1) to increase its expression levels and move into the nucleus. The reduction of DACH1 expression led to increased Smad2/3 phosphorylation but DACH1 overexpression resulted in decreased p-Smad2/3 and Smad4 protein levels. The glomerular expression of BMPR2 and DACH1 decreased in db/db mice which led to podocyte damage and albuminuria.
Conclusion
Hence BMPR2 and DACH1 form a protective pathway which maintains podocyte stability through TGF-β/Smad pathway suppression. The disruption of this pathway leads to podocyte injury through cytoskeletal damage and inflammatory responses which occur during the initial stages of DKD.
Funding
- Government Support – Non-U.S.