Diabetic nephropathy (DN) is one of the most serious complications of type I and type II diabetes. DN is characterized by hyperfiltration, hypertrophy, extracellular matrix accumulation, and proteinuria. This advances into renal fibrosis and loss of renal function. Reactive oxygen species (ROS) and TGF-beta have been implicated in the pathogenesis of diabetic nephropathy. Early stages of diabetic nephropathy are also associated with alterations in renal sodium handling as well as hypertension; both are processes linked by involvement of the arachidonic acid (AA) metabolites, 20-hydroxyeicosatetraenoic acid (20-HETE, produced by cytochrome P450-4a, (CYP4A) and epoxyeicosatrienoic acids (EETs). Indeed, metabolism of AA is increased in a rat model of diabetes. In this study, we demonstrate that rats with streptozotocin-induced diabetes of 1 month duration develop renal hypertrophy and increased fibronectin and TGF-beta1 expression/cortical levels concomitant with an increase in CYP4A expression and 20 HETE production. These results were also paralleled by an increase in reactive oxygen species (ROS) production and NADPH oxidase activity. Treatment of diabetic rats with HET0016, selective inhibitor of CYP 4A, prevented all these changes. Our results suggest that diabetes-induced induction of CYP4A and 20-HETE production could be a major pathophysiological mechanism leading to activation of ROS through an NADPH dependent pathway and TGF-beta1 thus resulting in major renal pathology. Inhibitors of 20-HETE production could thus have an important therapeutic potential in the treatment of diabetic nephropathy.
Download full-text PDF |
Source |
|---|
Publication Analysis
Top Keywords
Similar Publications
Therapeutic potential of stromal vascular fraction in early diabetic nephrotoxicity: a histomorphometric and immunohistochemical analysis in type 2 diabetes rat model.
Folia Morphol (Warsz)
January 2025
Department of Anatomy, Kasr El-Aini Faculty of Medicine, Cairo University, Cairo, Egypt, Egypt.
Background: Diabetic nephropathy (DN), a common complication of type 2 diabetes (T2D), significantly contributes to end-stage kidney disease (ESKD). Despite conventional treatments aimed at slowing disease progression, there is a pressing need for novel therapies. This study evaluates the potential therapeutic impact of adipose tissue derived stromal vascular fraction (SVF) on early diabetic nephrotoxicity in a rat model.
View Article and Find Full Text PDFFormula alleviates diabetic podocyte injury by regulating miR-21a-5p/FoxO1/PINK1-mediated mitochondrial autophagy.
Nan Fang Yi Ke Da Xue Xue Bao
January 2025
ZHANG Zhongjing School of Chinese Medicine, Rheumatology and Immunology, Nanyang Traditional Chinese Medicine Hospital, Nanyang 473004, China.
Objectives: To investigate the protective effect of Formula (YYHT) against high glucose-induced injury in mouse renal podocytes (MPC5 cells) and the possible mechanism.
Methods: Adult Wistar rats were treated with 19, 38, and 76 g/kg YYHT or saline via gavage for 7 days to prepare YYHT-medicated or blank sera for treatment of MPC5 cells cultured in high glucose (30 mmol/L) prior to transfection with a miR-21a-5p inhibitor or a miR-21a-5p mimic. The changes in miR-21a-5p expressions and the mRNA levels of FoxO1, PINK1, and Parkin in the treated cells were detected with qRT-PCR, and the protein levels of nephrin, podocin, FoxO1, PINK1, and Parkin were detected with Western blotting.
ACUTE HYPERGLYCEMIA INDUCES PODOCYTE APOPTOSIS BY MONOCYTE TNF-α RELEASE, A PROCESS ATTENUATED BY VITAMIN D AND GLP-1 RECEPTOR AGONISTS.
J Steroid Biochem Mol Biol
January 2025
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA; Department of Medicine, VA Medical Center, St. Louis, MO, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA. Electronic address:
Targeting optimal glycemic control based on hemoglobin A1c (A1c) values reduces but does not abolish the onset of diabetic kidney disease and its progression to chronic kidney disease (CKD). This suggests that factors other than the average glucose contribute to the residual risk. Vitamin D deficiency and frequent episodes of acute hyperglycemia (AH) are associated with the onset of albuminuria and CKD progression in diabetes.
View Article and Find Full Text PDFUbiquitination in diabetes and its complications: A perspective from bibliometrics.
World J Diabetes
January 2025
College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230012, Anhui Province, China.
Background: Diabetes has a substantial impact on public health, highlighting the need for novel treatments. Ubiquitination, an intracellular protein modification process, is emerging as a promising strategy for regulating pathological mechanisms. We hypothesize that ubiquitination plays a critical role in the development and progression of diabetes and its complications, and that understanding these mechanisms can lead to new therapeutic approaches.
View Article and Find Full Text PDFMizagliflozin ameliorates diabetes induced kidney injury by inhibitor inhibit inflammation and oxidative stress.
World J Diabetes
January 2025
Department of Nephrology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou 362000, Fujian Province, China.
Background: Mizagliflozin (MIZ) is a specific inhibitor of sodium-glucose cotransport protein 1 (SGLT1) originally developed as a medication for diabetes.
Aim: To explore the impact of MIZ on diabetic nephropathy (DN).
Methods: Diabetic mice were created using db/db mice.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!