Abstract: FR-OR036
Exosome-Derived TMEM106A Participates in Podocyte Injury via EGR1 in Preeclampsia
Session Information
- Glomerular Disease Outcomes: Measuring What Matters
November 07, 2025 | Location: Room 310A, Convention Center
Abstract Time: 05:50 PM - 06:00 PM
Category: Women's Health and Kidney Diseases
- 2200 Women's Health and Kidney Diseases
Authors
- Hu, Jinxiu, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Shen, Ning, Shandong University, Jinan, Shandong, China
- Lv, Zhimei, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
- Wang, Rong, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China
Background
Preeclampsia (PE), a pregnancy-specific hypertensive disorder, is the leading cause of maternal and fetal morbidity and mortality. Although renal complications, particularly podocyte injury, are hallmarks of preeclampsia-related organ dysfunction, the underlying mechanisms remain poorly understood.
Methods
PE patients from Gene Expression Omnibus database (GSE192902) and podocytes injury from (GSE124622) were used to select TMEM106A. real-time PCR was performed to detect the expression of TMEM106A in urine and plasm of PE patients. Spearman analysis was used to evaluate the correlation between urinary TMEM106A levels and podocyte injury. Plasma exosomes from PE patients were extracted, and stimulated podocytes. Real-time PCR, Western blot, and FITC-phalloidin staining were used to assess podocyte injury. Transcriptome sequencing in podocyte was performed to screen EGR1, the downstream gene of TMEM106A. AAV9 harboring TMEM106A mice and podocyte-specific EGR1 knockout mice were established in L-NAME-induced PE mouse model to observe fetal, placenta and kidney injury.
Results
TMEM106A is downregulated in both urine and plasm of PE patients and urinary TMEM106A level was positively correlated with nephrin and PCX, and negatively correlated with IL-1β and TNF-α. Compared with the controls, podocytes exposed to plasma exosomes from PE patients exhibit reduced TMEM106A levels and aggravate podocyte injury. In cultured podocytes, silence of TMEM106A aggravates cytoskeleton rearrangement and inflammation, while its overexpression alleviated these responses. Mechanistically, silence of TMEM106A promotes podocyte injury by upregulating EGR1. In vivo, TMEM106A overexpression alleviates renal injury in PE mouse, while podocyte-specific deletion of EGR1 protects against renal injury.
Conclusion
This study suggested that abnormal expression of exosome-derived TMEM106A induced podocyte injury via upregulating EGR1 in preeclampsia, which will be a potential approach for the treatment of renal dysfunction in PE.
Funding
- Government Support – Non-U.S.