Podocyte apoptosis in diabetic nephropathy by BASP1 activation of the p53 pathway via WT1
- 22 February 2021
- journal article
- research article
- Published by Wiley in Acta Physiologica
- Vol. 232 (1), e13634
- https://doi.org/10.1111/apha.13634
Abstract
Aims Diabetic nephropathy (DN) is a leading cause of end‐stage renal disease. BASP1 (brain acid‐soluble protein) is up‐regulated in podocyte‐specific protein phosphatase 2A knockout mice (Pod‐PP2A‐KO) that develop kidney dysfunction. Here, we explore the role of BASP1 for podocytes in DN. Methods BASP1 was assessed in kidneys from DN patients and DN mouse models, podocyte specific BASP1 knockout mice (Pod‐BASP1‐KO mice) were generated and studied in vivo. Furthermore, podocyte injury and apoptosis were measured after BASP1 knockdown and overexpression in a mouse podocyte cell line (MPC5). Potential signalling pathways involved in podocyte apoptosis were detected. Results BASP1 expression was up‐regulated in DN patients compared to normal controls. BASP1 specific deletion in podocytes protected against podocyte injury by reducing the loss of expression of slit diaphragm molecules and foot process effacement in the DN model. BASP1 promoted actin cytoskeleton rearrangements and apoptosis in the MPC5 podocyte line. Molecules involved in the p53 pathway were down‐regulated in BASP1 knockdown podocytes treated with high glucose compared to controls. BASP1 promoted podocyte apoptosis and P53 pathway activation through co‐repression with Wilms' tumour 1 transcription factor (WT1). Conclusion BASP1 activates the p53 pathway through modulation of WT1 to induce podocyte apoptosis in diabetic nephropathy.Keywords
Funding Information
- Natural Science Foundation of Zhejiang Province (LQ18H050001, LQ19H050007)
- Deutsche Forschungsgemeinschaft (394046635‐SFB 1365)
This publication has 50 references indexed in Scilit:
- New Experimental Models of Diabetic Nephropathy in Mice Models of Type 2 Diabetes: Efforts to Replicate Human NephropathyExperimental Diabetes Research, 2012
- FOXO3 signalling links ATM to the p53 apoptotic pathway following DNA damageNature Communications, 2012
- Unmet Need in Renal Protection – Do We Need a More Comprehensive Approach?Contributions to nephrology, 2011
- BASP1 Promotes Apoptosis in Diabetic NephropathyJournal of the American Society of Nephrology, 2010
- Tumour suppression by p53: a role for the DNA damage response?Nature Reviews Cancer, 2009
- Dynamic interaction between WT1 and BASP1 in transcriptional regulation during differentiationNucleic Acids Research, 2008
- Podocytes in culture: past, present, and futureKidney International, 2007
- iTRAQ Is a Useful Method To Screen for Membrane-Bound Proteins Differentially Expressed in Human Natural Killer Cell TypesJournal of Proteome Research, 2006
- Spatial segregation of transport and signalling functions between human endothelial caveolae and lipid raft proteomesBiochemical Journal, 2006
- BASP1 Is a Transcriptional Cosuppressor for the Wilms' Tumor Suppressor Protein WT1Molecular and Cellular Biology, 2004