Cabin1 involves in renal tubular epithelial cells mitochondrial dysfunction through SIRT1/p53 pathway

Area of Science:

• Nephrology
• Cell Biology
• Molecular Biology

Background:

• Angiotensin II (AngII) significantly increases Calcineurin binding protein 1 (Cabin1) expression during renal tubular epithelial cell (RTEC) injury.
• The precise role of Cabin1 in RTEC remains incompletely understood.

Purpose of the Study:

• To investigate the downstream targets and function of Cabin1 in an in vitro model of RTEC injury.
• To elucidate the molecular mechanisms underlying Cabin1's role in AngII-induced RTEC damage.

Main Methods:

• Primary rat kidney epithelial cells were cultured and treated with AngII.
• Mitochondrial morphology was assessed using electron microscopy.
• Cytoskeleton and Cabin1 distribution were visualized via immunofluorescence staining.
• Protein expression levels (Cabin1, p53, Cytochrome C, SIRT1) were quantified using Western blot analysis.
• Cabin1 knockdown was performed to evaluate its functional impact.

Main Results:

• AngII induced cytoskeletal disruption and Cabin1 overexpression in RTEC.
• Mitochondria exhibited abnormal morphology (increased aspect ratio) following AngII stimulation.
• Cabin1 knockdown aggravated AngII-induced mitochondrial abnormalities.
• AngII treatment led to increased Cabin1, p53, and Cytochrome C, with decreased SIRT1.
• Cabin1 knockdown further decreased SIRT1 and increased p53 and Cytochrome C levels.

Conclusions:

• Cabin1 plays a crucial role in AngII-induced RTEC mitochondrial dysfunction.
• The SIRT1/p53 signaling pathway is implicated in Cabin1's mechanism of action.
• Cabin1 emerges as a potential novel biomarker for RTEC injury.