Serum and glucocorticoid-inducible kinase 3 (SGK3) is involved in maintaining podocyte function by regulating the protein levels of podocin and CD2-associated protein. Nephrin is also one of the slit diaphragm proteins of podocytes, but whether SGK3 participates in podocyte injury by regulating the levels of nephrin remains unclear. In this study, we focused on whether SGK3 affects nephrin levels and the mechanisms involved in the same. In the kidneys of adriamycin (ADR)-induced podocyte injury mouse model, the protein levels of SGK3 and nephrin were significantly decreased. Furthermore, the expression of SGK3 was negatively correlated with the output of proteinuria, and positively correlated with the levels of nephrin. In ADR-treated conditionally immortalized mouse podocyte cells (MPCs), the protein levels of nephrin and SGK3 were inhibited, while the constitutive expression of SGK3 reversed the ADR-induced decline in nephrin protein levels. Furthermore, ADR treatment or SGK3 inactivation enhanced the ubiquitin-proteasome degradation of nephrin in MPCs, and dramatically activated downstream effector proteins of SGK3, neural precursor cells expressing developmentally downregulated protein 4 subtype 2 (Nedd4-2) and glycogen synthase kinase-3 β (GSK3β). Similarly, Nedd4-2 or GSK3β overexpression resulted in increased activity of Nedd4-2 or GSK3β, and significantly downregulated nephrin levels. Interestingly, ubiquitin-mediated protein degradation of nephrin was regulated by Nedd4-2, rather than by GSK3β. In summary, SGK3 inactivation downregulated the levels of nephrin by increasing Nedd4-2 and GSK3β activity in ADR-induced podocyte injury model; in particular, the SGK3/Nedd4-2 signaling pathway was found to be involved in ubiquitin-mediated proteasome degradation of nephrin.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8811367 | PMC |
http://dx.doi.org/10.3389/fphys.2021.810473 | DOI Listing |
Curr Stem Cell Res Ther
December 2024
National Institute for Drug Clinical Trial, Beijing Tongren Hospital, Capital Medical University, No.1 Dongjiaominxiang Road, Beijing, 100730, China.
Background: Idiopathic Nephrotic Syndrome (INS) is a common kidney disease in children, and the main clinical manifestations are hypoproteinaemia, proteinuria, hyperlipidaemia, and oedema. Mesenchymal Stem Cells (MSCs) are involved in tissue repair, protection against fibrosis, and immune modulation but have rarely been studied in INS.
Objective: This study aimed to explore the therapeutic potential of stem cells derived from human exfoliated deciduous teeth (SHEDs) in INS using an adriamycin-induced nephropathy (AN) rat model.
Int Immunopharmacol
December 2024
Department of Nephrology, Shanxi Provincial People's Hospital, The Fifth Clinical Medical College of Shanxi Medical University, 29 Shuang Ta East Street, Taiyuan 030012, China. Electronic address:
Background: Effective therapeutic approaches for the treatment of diabetic nephropathy (DN) with irreversible deterioration of renal function are currently lacking. In this study, we aimed to investigate the ability of the glucagon-likepeptide-1 (GLP-1)/ gastric inhibitory polypeptide (GIP) dual agonist, tirzepatide to alleviate DN in mice and its underlying mechanisms.
Methods: We investigated the reno-protective effect of semaglutide and tirzepatide in a mouse model of DN, an insulin-treated positive control group was also included.
Transl Androl Urol
November 2024
Internal Medical Department, the First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine, Guangzhou, China.
Background: Diabetic nephropathy (DN), a severe complication of diabetes, is characterized by glomerular and tubular damage, which often leads to end-stage renal disease (ESRD). The role of renal macrophages (Mφs), particularly their phenotypic plasticity and function in DN, remains poorly understood. This study investigated the key factors influencing Mφ polarization and their impact on podocyte (PODO) injury in DN.
View Article and Find Full Text PDFCrit Care
December 2024
Division of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA.
Background: Patients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of Nephrology, the First Affiliated Hospital of Zhejiang Chinese Medical University (Zhejiang Provincial Hospital of Chinese Medicine), Hangzhou, Zhejiang 310000, China; Provincial Key Laboratory for Research and Translation on the Syndrome of Kidney Deficiency Accompanied by Blood Stasis and Turbidity, China. Electronic address:
High glucose (HG)-mediated podocyte damage can be ameliorated by lncRNA HOXB3OS, and exosomes derived from adipose-derived mesenchymal stem cells (ADSCs-Exo) can ameliorate the progression of diabetic kidney disease (DKD) dependening on RNA. To investigate the mechanism by which HOXB3OS improves podocyte injury and the effects of engineered ADSCs-Exo with a high abundance of HOXB3OS on DKD progression, MPC5 cells stimulated with HG and db/db mice were used to develop a podocyte injury model and type II DKD mouse model, respectively. HOXB3OS expression and mRNA level of SIRT1 were detected by qRT-PCR.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!