Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Inflammation ; 45(3): 992-1006, 2022 Jun.
Article in English | MEDLINE | ID: mdl-34783942

ABSTRACT

Hyperglycemia-induced oxidative stress in podocytes exerts a major role in the pathological process of diabetic nephropathy. Tripartite motif-containing protein 32 (TRIM32) has been reported to be a key protein in the modulation of cellular apoptosis and oxidative stress under various pathological processes. However, whether TRIM32 participates in the regulation of high glucose (HG)-induced injury in podocytes has not been investigated. This work aimed to assess the possible role of TRIM32 in mediating HG-induced apoptosis, oxidative stress, and inflammatory response in podocytes in vitro. Our results showed a marked increase in TRIM32 expression in HG-exposed podocytes and the glomeruli of diabetic mice. Loss-of-function experiments showed that TRIM32 knockdown improves the viability of HG-stimulated podocytes and suppresses HG-induced apoptosis, oxidative stress, and inflammatory responses in podocytes. Further investigation revealed that TRIM32 inhibition enhances the activation of nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, which is associated with the modulation of the Akt/glycogen synthase kinase-3ß (GSK-3ß) axis in podocytes following HG exposure. However, Akt suppression abrogated the TRIM32 knockdown-mediated activation of Nrf2 in HG-exposed podocytes. Nrf2 knockdown also markedly abolished the protective effects induced by TRIM32 inhibition o in HG-exposed podocytes. In summary, this work demonstrated that TRIM32 inhibition protects podocytes from HG-induced injury by potentiating Nrf2 signaling through modulation of Akt/GSK-3ß signaling. The findings reveal the potential role of TRIM32 in mediating podocyte injury during the progression of diabetic nephropathy.


Subject(s)
Diabetes Mellitus, Experimental , Diabetic Nephropathies , Podocytes , Transcription Factors , Tripartite Motif Proteins , Ubiquitin-Protein Ligases , Animals , Apoptosis , Diabetes Mellitus, Experimental/metabolism , Diabetic Nephropathies/metabolism , Glucose/metabolism , Glucose/toxicity , Glycogen Synthase Kinase 3 beta/metabolism , Humans , Mice , NF-E2-Related Factor 2/metabolism , Oxidative Stress/physiology , Podocytes/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Transcription Factors/metabolism , Tripartite Motif Proteins/metabolism , Ubiquitin-Protein Ligases/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...