Abstract: FR-PO987
BCL2 Associated Athanogene 2 (BAG2) Mediates Kidney Fibrosis Through TGF-β1 Signaling Pathway
Session Information
- CKD: Pathobiology - I
November 04, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
Category: CKD (Non-Dialysis)
- 2203 CKD (Non-Dialysis): Mechanisms
Authors
- Sung, Min ji, CHA University - Bundang Campus, Seongnam, Gyeonggi-do, Korea (the Republic of)
- An, Hyun-Ju, CHA University - Bundang Campus, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Ha, Min Heui, CHA University - Bundang Campus, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Jeong, Hyeyun, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Lee, Yu ho, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Yang, Taeyoung, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Yang, Dong Ho, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
- Lee, So-young, CHA Bundang Medical Center, Seongnam, Gyeonggi-do, Korea (the Republic of)
Background
Kidney fibrosis, regardless of its etiology, is the inevitable consequence of almost chronic kidney diseases. Transforming growth factor-β1 (TGF-β1) plays a central role in kidney fibrotic disease. Therefore, it is important to find novel targets that regulate TGF-β1 signaling. An increasing number of studies have revealed that BAG2 is involved in the pathogenesis of various diseases, including cancer. However, the regulatory mechanisms of BAG2 in kidney fibrosis remain unclear.
Methods
Expression of BAG2 was validated by western blot, RT-PCR and FACS in unilateral ureteral obstruction (UUO) and adenine-diets WT or BAG2 knockout mouse model. The molecular mechanism study was performed in TGF-β1-induced human kidney proximal tubular cells (HKC-8) cells by gene expression analysis, and BAG2 lentiviral knockdown and overexpression cell lines. Human serums were isolated from patients with renal failure and healthy controls and BAG2 expression level was detected by ELISA.
Results
In the Kidney fibrosis mouse model, mRNA and protein showed that compared with the control group, the expressions of BAG2, and fibrotic marker were all increased, FACS analysis also shows that BAG2 increased during fibrotic changes. At the same time, overexpression of BAG2 suppressed enhancements on epithelial to mesenchymal transition and fibrosis via the TGF-β1 / SMAD3 / BAG2 complex. Also, BAG2 was increased in serum from chronic kidney disease patients.
Conclusion
This is, to our knowledge, the first report about the function of BAG2 in kidney fibrosis. These results demonstrate that BAG2 regulates kidney fibrosis via the TGF-β1 signaling and suggest that BAG2 is a potential therapeutic target for the treatment of kidney fibrosis.
Funding
- Government Support – Non-U.S.