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Published on: July 2, 2020
Knocking down Cabin1 induces glomerular podocyte injury
Yueqiang Wen1, Lingling Liu2, Qingdong Xu3
1Department of Nephrology, The Second Affiliated Hospital, GuangZhou Medical University, 250th, Chang Gang East Road, Guangzhou, 510260, China. yueqiangwen@163.com.
Background:
Podocyte damage exerts a key role in proteinuria. We have demonstrated that calcineurin-binding protein 1 (Cabin1) upregulated during podocyte injury, yet its function in podocyte is still unclear.
Methods:
We established 5/6 nephrectomized rats and angiotensin II (AngII)-injured podocyte, as well as knocked down Cabin1 with siRNA in cultured podocytes. Rats were killed at 4 or 8 weeks after 5/6 nephrectomy. The localization of podocyte cytoskeleton was detected after immunofluorescence staining. Podocyte mitochondrial morphology was observed under electron microscopy. Podocyte mitochondrial transmembrane potential (MMP) was measured with MitoCapture kit. Cabin1 and cytochrome c protein expression were detected by western blot.
Results:
Massive proteinuria, as well as obvious segmental glomerular sclerosis, was found in rats at 8 weeks after nephrectomy, accompanied with the disruption of synaptopodin. Moreover, mitochondria changed from large and ellipsoid shape to the small, long, and irregular shape in rats at 4 weeks after operation. At 8 weeks, mitochondria were swollen and cristae were remarkably dissolved. Compared to sham-operated rats, Cabin1 protein expression was obviously upregulated in rats at 8 weeks. AngII induced the decrease in MMP, as well as the overexpression of Cabin1 and cytochrome c protein in podocytes. Knocking down Cabin1 induced the disruption of F-actin and overexpression of cytochrome c (1.81 ± 0.21 in siRNA group vs. 0.86 ± 0.11 in negative control group).
Conclusions:
Knocking down Cabin1 induces the disruption of cytoskeleton and mitochondrial dysfunction in podocyte. Cabin1 could be a crucial factor in podocyte damage.
Insights
Calcineurin-binding protein 1 (Cabin1) disruption damages podocyte cytoskeleton and mitochondria, contributing to kidney disease. Cabin1 plays a crucial role in podocyte injury and proteinuria.
Area of Science:
- Nephrology
- Cell Biology
- Molecular Medicine
Background:
- Podocyte damage is central to proteinuria development.
- Calcineurin-binding protein 1 (Cabin1) is upregulated in podocyte injury, but its function remains unknown.
Purpose of the Study:
- To investigate the role of Cabin1 in podocyte injury and its impact on cytoskeleton and mitochondrial function.
Main Methods:
- Utilized 5/6 nephrectomized rat model and angiotensin II (AngII)-induced podocyte injury.
- Investigated Cabin1 knockdown using siRNA in cultured podocytes.
- Assessed podocyte cytoskeleton, mitochondrial morphology, mitochondrial transmembrane potential (MMP), and protein expression via immunofluorescence, electron microscopy, and western blot.
Main Results:
- Nephrectomized rats exhibited proteinuria, glomerular sclerosis, and disrupted synaptopodin.
- Podocyte mitochondria showed morphological changes and dysfunction (decreased MMP) post-injury.
- Cabin1 knockdown exacerbated cytoskeleton disruption and mitochondrial dysfunction, indicated by increased cytochrome c release.
Conclusions:
- Cabin1 knockdown leads to podocyte cytoskeleton disruption and mitochondrial dysfunction.
- Cabin1 is identified as a critical factor in mediating podocyte damage and progression of kidney disease.
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