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The Role of TLR4 on PGC-1α-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease
Joint Authors
Shuguang, Yuan
Yuan, Shuguang
Liu, Xuemei
Qu, Zhong
Gong, Zailiang
Li, Jun
Xiao, Li
Yang, Yuan
Liu, Hong
Liu, Fuyou
Sun, Lin
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2018, Issue 2018 (31 Dec. 2018), pp.1-14, 14 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2018-05-16
Country of Publication
Egypt
No. of Pages
14
Main Subjects
Abstract EN
The role and precise mechanism of TLR4 in mitochondria-related oxidative damage and apoptosis of renal tubules in diabetic kidney disease (DKD) remain unclear.
We examined the expression of TLR4 in renal biopsy tissues.
Db/db diabetic mice and HK-2 cells cultured under high glucose (HG) were used as in vivo and vitro models.
Real-time RT-PCR, Western blot, and immunohistochemistry were performed to examine the mRNA and protein levels of TLR4, NF-κΒ, PGC-1α, cytochrome C, and cleaved caspase-3.
ATP level, activity of electron transport chain complex III, and antioxidant enzymes were investigated for mitochondrial function.
Electron microscopy (EM) and MitoTracker Red CMXRos were used for mitochondrial morphology alteration.
DHE staining and TUNEL assay were detected for ROS accumulation and apoptosis.
PGC-1α plasmids were used for the overexpression of PGC-1α in HK-2.
TAK242 and parthenolide were used as TLR4 and NF-κB blockers, respectively.
Results showed that TLR4 was extensively expressed in the renal tubules of DKD patients and db/db diabetic mice, which was positively related to the tubular interstitial damage score and urinary β-NAG levels.
In diabetic mice, inhibition of TLR4 could reverse the decreased expression of PGC-1α, increased expression of cytochrome C and cleaved caspase-3, mitochondrial dysfunction and deformation, increased accumulation of ROS, and activation of tubular cell apoptosis.
In vitro, inhibition of TLR4 or NF-κB showed consistent results.
PGC-1α overexpression could reverse the mitochondrial dysfunction, increased cleaved caspase-3, and apoptosis in HK-2 cells treated with HG.
Data indicated that the TLR4/NF-κB signaling pathway might be the upstream pathway of PGC-1α and promote the tubular damage of DKD by modulating the mitochondria-related oxidative damage and apoptosis.
American Psychological Association (APA)
Yuan, Shuguang& Liu, Xuemei& Shuguang, Yuan& Qu, Zhong& Gong, Zailiang& Li, Jun…[et al.]. 2018. The Role of TLR4 on PGC-1α-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease. Oxidative Medicine and Cellular Longevity،Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1211783
Modern Language Association (MLA)
Yuan, Shuguang…[et al.]. The Role of TLR4 on PGC-1α-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease. Oxidative Medicine and Cellular Longevity No. 2018 (2018), pp.1-14.
https://search.emarefa.net/detail/BIM-1211783
American Medical Association (AMA)
Yuan, Shuguang& Liu, Xuemei& Shuguang, Yuan& Qu, Zhong& Gong, Zailiang& Li, Jun…[et al.]. The Role of TLR4 on PGC-1α-Mediated Oxidative Stress in Tubular Cell in Diabetic Kidney Disease. Oxidative Medicine and Cellular Longevity. 2018. Vol. 2018, no. 2018, pp.1-14.
https://search.emarefa.net/detail/BIM-1211783
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1211783