Advanced Oxidation Protein Products Aggravate Tubulointerstitial Fibrosis Through Protein Kinase C-Dependent Mitochondrial Injury in Early Diabetic Nephropathy

Antioxidants & Redox Signaling
Xiao LiXiaoyan Bai

Abstract

Diabetic nephropathy (DN) is the most common microvascular complications and the principal cause of mortality and morbidity rates in patients with diabetes. The expression of advanced oxidation protein products (AOPPs) has been found in vacuolated renal tubules in DN and correlated with patients' decreased renal function. The accumulation of AOPPs is regarded as an initiating factor in podocyte injuries via the protein kinase C (PKC) signaling, which plays a critical role in triggering oxidative stress and mitochondrial injuries in diseases including DN. Whether AOPPs could induce mitochondrial injuries and fibrosis in renal tubules remains largely unknown. Herein, we tested the hypothesis that the accumulation of AOPPs in diabetes incurs mitochondrial dysfunction and oxidative stress, causing renal tubulointerstitial fibrosis (TIF) via PKC signaling pathway. In vivo, intrarenal AOPPs accumulation correlated with oxidative stress, renal fibrosis, proteinuria, and declined renal function in DN patients and diabetic rats. AOPPs-induced mitochondrial injuries, apoptosis, and TIF were significantly mitigated by PKCη inhibition in diabetic rats. In vitro, high glucose (HG) stimulated AOPP expression and augmented PKC-mediated oxidat...Continue Reading

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Citations

Apr 16, 2020·International Journal of Molecular Sciences·Lucas Opazo-RíosJesús Egido
Dec 19, 2020·Molecular Therapy. Nucleic Acids·Yuxin XieDongshan Zhang
Apr 17, 2021·Frontiers in Medicine·Jingsheng ChangYifei Zhong

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Methods Mentioned

BETA
biopsy
transmission electron microscopy
Coimmunoprecipitation
flow cytometry
RSA
enzyme-linked immunosorbent assay
ELISA
transfection
Protein Assay
reverse transcription-PCR

Software Mentioned

ModFit
SPSS
Image J
CellQuest Pro
Cell Quest

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