Abstract: TH-PO0368
Role of OSBPL7 in Lipid-Mediated Glomerular Injury and Senescence in Alport Syndrome
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
- Khuu, Nicholas, University of Miami Miller School of Medicine, Miami, Florida, United States
- Njeim, Rachel, University of Miami Miller School of Medicine, Miami, Florida, United States
- Insenga, Arianna, University of Miami Miller School of Medicine, Miami, Florida, United States
- Molina David, Judith T., University of Miami Miller School of Medicine, Miami, Florida, United States
- Merscher, Sandra, University of Miami Miller School of Medicine, Miami, Florida, United States
- Fornoni, Alessia, University of Miami Miller School of Medicine, Miami, Florida, United States
Background
Alport Syndrome (AS) is a hereditary type IV collagen disorder that causes progressive glomerular injury and chronic kidney disease. Although basement membrane disruption is central to AS, the pathways linking extracellular matrix defects to the podocyte remains incompletely defined. We have previously demonstrated that lipid droplet (LD) accumulation and impaired cholesterol handling contributes to podocyte dysfunction in proteinuric kidney disease. Further, we identified OSBPL7, an oxysterol-binding protein implicated in ABCA1-dependent cholesterol efflux, as a therapeutic target in a screen of ABCA1 inducers, and that knockdown of OSBPL7 increases cholesterol efflux in AS models. Therefore, we hypothesize that dysregulation of OSBPL7 contributes to maladaptive lipid remodeling, resulting in organelle stress and senescence in AS podocytes.
Methods
OSBPL7 expression was evaluated in Col4a3-/- mouse podocytes and kidney cortices as a model of AS. Immortalized mouse (AS/WT) and human podocytes (WT) were transduced with CRISPR-Cas9 mediated knockout of OSBPL7 and an OSBPL7 overexpression construct to test whether perturbation of OSBPL7 alters lipid handling in AS models. LD abundance was assessed by neutral lipid staining and high-content imaging. Senescence and other markers of cellular stress were assessed by senescence-associated β-galactosidase staining, RT-qPCR, and immunoblotting.
Results
OSBPL7 expression was increased in AS podocytes and kidney cortices. These changes occurred in association with increased senescence-associated signaling, including p53/21 pathway activation and elevated senescence-associated β-galactosidase activity. Preliminary analyses from Osbpl7 and Col4a3 double knockout podocytes demonstrate altered lipid droplet patterns. Together, these findings suggest that AS podocytes demonstrate a senescent phenotype and that OSBPL7 may functionally contribute to lipid-driven stress responses in AS.
Conclusion
AS podocytes demonstrated increased expression of OSBPL7, LD accumulation and senescence-like programming in AS. We further show that OSBPL7 knockout alters LD patterns. These preliminary data support that AS promotes lipid remodeling through OSBPL7-dependent pathways, potentially contributing to progressive glomerular injury. Targeting OSBPL7-mediated lipid handling may represent a strategy to reduce podocyte stress and slow CKD progression in AS.