Advanced glycation end products-mediated hypertrophy is negatively regulated by tetrahydrobiopterin in renal tubular cells

2012 ◽  
Vol 355 (1) ◽  
pp. 71-77 ◽  
Author(s):  
Yi-Chen Liao ◽  
Ying-Ho Lee ◽  
Lea-Yea Chuang ◽  
Jinn-Yuh Guh ◽  
Ming-Der Shi ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

scholarly journals Soluble receptor for advanced glycation end products protects from ischemia- and reperfusion-induced acute kidney injury

Biology Open ◽  
2021 ◽  
Author(s):  
Taro Miyagawa ◽  
Yasunori Iwata ◽  
Megumi Oshima ◽  
Hisayuki Ogura ◽  
Koichi Sato ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Advanced Glycation End Products ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Tubular Damage ◽  
Advanced Glycation ◽  
Renal Tubular Damage ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

The full-length receptor for advanced glycation end products (RAGE) is a multiligand pattern recognition receptor. High-mobility group box 1 (HMGB1) is a RAGE ligand of damage-associated molecular patterns that elicits inflammatory reactions. The shedded isoform of RAGE and endogenous secretory RAGE (esRAGE), a splice variant, are soluble isoforms (sRAGE) that act as organ-protective decoys. However, the pathophysiologic roles of RAGE/sRAGE in acute kidney injury (AKI) remain unclear. We found that AKI was more severe, with enhanced renal tubular damage, macrophage infiltration, and fibrosis, in mice lacking both RAGE and sRAGE than in wild-type control mice. Using murine tubular epithelial cells (TECs), we demonstrated that hypoxia upregulated messenger RNA (mRNA) expression of HMGB1 and tumor necrosis factor α (TNF-α), whereas RAGE and esRAGE expressions were paradoxically decreased. Moreover, the addition of recombinant sRAGE canceled hypoxia-induced inflammation and promoted cell viability in cultured TECs. sRAGE administration prevented renal tubular damage in models of ischemia/reperfusion-induced AKI and of anti-glomerular basement membrane (anti-GBM) glomerulonephritis. These results suggest that sRAGE is a novel therapeutic option for AKI.

HMGB1 Enhances the AGE-Induced Expression of CTGF and TGF-β via RAGE-Dependent Signaling in Renal Tubular Epithelial Cells

2015 ◽  
Vol 41 (3) ◽  
pp. 257-266 ◽  
Author(s):  
Meichu Cheng ◽  
Hong Liu ◽  
Dongshan Zhang ◽  
Yinghong Liu ◽  
Chang Wang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Advanced Glycation End Products ◽  
Tubular Epithelial Cells ◽  
Advanced Glycation ◽  
Induced Expression ◽  
Mesenchymal Transition ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

Background/Aims: Advanced glycation end products (AGEs) induce epithelial mesenchymal transition (EMT) in renal proximal tubular epithelial cells (PTECs) by promoting the two EMT regulators, transforming growth factor beta (TGF-β) and connective tissue growth factor (CTGF). However, the exact signaling mechanism remains largely unclear. Methods: We investigated the promotion to high mobility group box 1 (HMGB1) in renal tubular epithelial HK-2 cells by AGE-BSA with quantitative PCR and western blot assay, and then determined the regulatory role of HMGB1 in the AGE-BSA-induced CTGF and TGF-β. In addition, the dependence of the receptor of advanced glycation end products (RAGE) was also examined in the CTGF and TGF-β promotion by AGEs and HMGB1 in HK-2 cells using the RNAi method. Results: It was demonstrated that AGEs induced translocation and release of HMGB1 from tubular epithelial HK-2 cells, and the released HMGB1 enhanced the promotion to CTGF and TGF-β by AGEs in HK-2 cells. On the other side, the HMGB1 knockdown by siRNA attenuated the AGE-BSA-induced expression of TGF-β. Moreover, the CTGF and TGF-β promotion in HK-2 cells by AGEs and HMGB1 was RAGE-dependent. Conclusion: Our results indicated that AGEs induced HMGB-1 and promoted the CTGF and TGF-β in renal epithelial HK-2 cells RAGE-dependently. And there was a synergism between AGEs and HMGB1 in the RAGE signaling activation. The in vitro data suggested that the AGE-RAGE and HMGB-1-RAGE signaling might play an important role in the promotion of CTGF and TGF-β in the renal fibrosis process of diabetic nephropathy.

scholarly journals Regulation of heparanase by albumin and advanced glycation end products in proximal tubular cells

2011 ◽  
Vol 1813 (8) ◽  
pp. 1475-1482 ◽  
Author(s):  
Valentina Masola ◽  
Giovanni Gambaro ◽  
Elena Tibaldi ◽  
Maurizio Onisto ◽  
Cataldo Abaterusso ◽  
...  
Keyword(s):  
Advanced Glycation End Products ◽  
Advanced Glycation ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Glycation End Products ◽  
End Products ◽  
Proximal Tubular

scholarly journals Update on Mechanisms of Renal Tubule Injury Caused by Advanced Glycation End Products

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Hong Sun ◽  
Yang Yuan ◽  
Zilin Sun
Keyword(s):  
Advanced Glycation End Products ◽  
Lipid Accumulation ◽  
Cholesterol Efflux ◽  
Cholesterol Synthesis ◽  
Renal Tubule ◽  
Foam Cell Formation ◽  
Advanced Glycation ◽  
Glycation End Products ◽  
End Products ◽  
Renal Tubular

Diabetic nephropathy (DN) caused by advanced glycation end products (AGEs) may be associated with lipid accumulation in the kidneys. This study was designed to investigate whether Nε-(carboxymethyl) lysine (CML, a member of the AGEs family) increases lipid accumulation in a human renal tubular epithelial cell line (HK-2) via increasing cholesterol synthesis and uptake and reducing cholesterol efflux through endoplasmic reticulum stress (ERS). Our results showed that CML disrupts cholesterol metabolism in HK-2 cells by activating sterol regulatory element-binding protein 2 (SREBP-2) and liver X receptor (LXR), followed by an increase in 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoAR) mediated cholesterol synthesis and low density lipoprotein receptor (LDLr) mediated cholesterol uptake and a reduction in ATP-binding cassette transporter A1 (ABCA1) mediated cholesterol efflux, ultimately causing lipid accumulation in HK-2 cells. All of these responses could be suppressed by an ERS inhibitor, which suggests that CML causes lipid accumulation in renal tubule cells through ERS and that the inhibition of ERS is a potential novel approach to treating CML-induced renal tubular foam cell formation.

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