Oxysterol-Binding Protein-Like 7 Deficiency in CKD
- Glomerular Diseases: Podocyte Biology - I
November 02, 2023 | Location: Exhibit Hall, Pennsylvania Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1403 Podocyte Biology
- Pressly, Jeffrey D., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Schiffer, Mario, Universitatsklinikum Erlangen Medizinische Klinik 4 Nephrologie und Hypertensiologie, Erlangen, Bayern, Germany
- Merscher, Sandra M., University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
- Fornoni, Alessia, University of Miami Katz Family Division of Nephrology and Hypertension, Miami, Florida, United States
OSBPs have been implicated in various processes such as cholesterol transfer from the endoplasmic reticulum to the Golgi, and cholesterol efflux. Previous studies have shown that OSBPL7 deficiency leads to decreased autophagy in other cell types, which may impact lipid trafficking and podocyte function. The purpose of this study is to investigate the role of OSBPL7 in chronic kidney disease and its potential as a therapeutic target. OSBPL7's involvement in autophagy and endoplasmic reticulum stress suggests that its deficiency may contribute to the development of CKD.
The study utilized immortalized mouse podocytes and a Tg[l-fabp:DBP:eGFP] zebrafish model to investigate the effects of OSBPL7 deficiency on the development of renal dysfunction in podocyte disease and measure the integrity of glomerular filtration. We determined OSBPL7 protein levels in metabolic and non-metabolic mouse models of CKD using western blot. OSBPL7 deficient podocytes and zebrafish were generated and the impact of OSBPL7 deficiency on ER stress markers, autophagy, lipid droplets, and proteinuria was analyzed.
The results show that OSBPL7 protein levels were reduced in the renal cortex of metabolic and non-metabolic mouse models of CKD. OSBPL7 deficiency leads to an increase in apoptosis levels and ER stress markers in podocytes and a decrease in autophagic flux. Additionally, an increase in lipid droplet levels is observed in OSBPL7 deficient podocytes, but this increase was found to be cholesterol independent. Knocking down OSBPL7 expression in Tg[l-fabp:DBP:eGFP] zebrafish leads to increased proteinuria and a slight edema phenotype. The findings suggest that OSBPL7 plays a critical role in the regulation of autophagy and ER stress in podocytes and contributes to the progression of CKD.
This study sheds light on the important role of OSBPL7 in podocytes and its potential as a therapeutic target in CKD. The results indicate that OSBPL7 deficiency may lead to lipid accumulation inside the podocyte and contribute to the proteinuria observed in CKD. Further studies are needed to fully understand the mechanisms and to develop potential therapeutic strategies for treating CKD. In summary, this study provides new insights into the role of OSBPL7 in chronic kidney disease and directly implicated OSBPL7 deficiency to proteinuria in a zebrafish model.
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