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A vital role for Angptl3 in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro
- Source :
- BMC Nephrology
- Publisher :
- Springer Nature
-
Abstract
- Background Podocyte detachment and apoptosis are two risk factors causing podocyte loss, F-actin rearrangement is involved in detachment and apoptosis. However, the nature of events that promote detachment and apoptosis of podocytes and whether detachment occurred simultaneously with apoptosis are still unclear. Previously, it was found that angiopoietin-like3 (Angptl3) induces F-actin rearrangement in podocytes. In this study we investigate whether Angptl3 influences podocyte loss (detachment and apoptosis) and the process through which Angptl3 exactly influenced the podocyte loss. Methods In conditionally immortalized mice podocytes, recombinant mice Angptl3 protein (rm-Angptl3) was used to mimic Angptl3 overexpression model and transfection with small interfering RNA (siRNA) to knockdown the expression of Angptl3. Both flow cytometry analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay were used to detect apoptosis. Rearrangement of F-actin was assessed using confocal microscopy. Western blot assay was used to measure levels of Angptl3, integrin α3β1, integrin-linked kinase (ILK), p53, caspase 3, and phosphorylation of integrin β1. Results In a puromycin aminonucleoside (PAN)-induced podocyte injury model, rm-Angptl3 accelerated the loss of podocytes, both detachment and apoptosis occurred, and F-actin rearrangement is involved in the process. However, knockdown of Angptl3 by siRNA markedly ameliorated these injuries. Observed effects were partially correlated with the altered integrin α3β1, ILK and p53, rather than caspase 3. Conclusions Angptl3 is a novel factor involved in the PAN-induced podocyte loss by affecting detachment and apoptosis in vitro. This study helps to deepen the understanding of the mechanisms of podocyte loss and lays the foundation for developing a new successful therapy for podocyte injury via lower expression of Angptl3.
- Subjects :
- Male
Angptl3
medicine.medical_specialty
Detachment
Podocyte loss
Blotting, Western
Fluorescent Antibody Technique
Apoptosis
Enzyme-Linked Immunosorbent Assay
Puromycin Aminonucleoside
Transfection
Sensitivity and Specificity
Podocyte
Mice
Angiopoietin-like Protein
Internal medicine
ANGPTL3
Animals
Medicine
RNA, Small Interfering
Cells, Cultured
Angiopoietin-Like Protein 3
Mice, Knockout
F-actin rearrangement
Podocytes
business.industry
Role
Flow Cytometry
In vitro
Cell biology
Blot
Angiopoietin-like Proteins
medicine.anatomical_structure
Nephrology
Immunology
business
Angiopoietins
Biomarkers
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 14712369
- Volume :
- 16
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- BMC Nephrology
- Accession number :
- edsair.doi.dedup.....93885107732f26e63bef4f65cdad5ed4
- Full Text :
- https://doi.org/10.1186/s12882-015-0034-4