Albumin-stimulated DNA synthesis is mediated by Ca<sup>2+</sup>/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-κB signal pathways in renal proximal tubule cells

Lee, Yu Jin; Han, Ho Jae

doi:10.1152/ajprenal.00408.2007

Cited by 23 publications

(22 citation statements)

References 42 publications

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“…These observations are consistent with previous results that demonstrated that cells under ER stress can stave off apoptosis by activating JNK (38) or NF-B (50). Our previous report (27) showed that MAPKs and NF-B activation are involved in the regulation of SGLTs in PTCs, in which NF-B phosphorylation stimulated by p44/42 MAPKs, p38 MAPK, and JNK activations is responsible for the increases of SGLT expression. In addition, p44/42 MAPKs are an important downstream effector mechanism for cellular protection by ER stress in renal epithelial cells (18).…”

Section: Discussionmentioning

confidence: 96%

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Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Lee¹,

Han²

2009

American Journal of Physiology-Renal Physiology

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Recent studies demonstrated that endoplasmic reticulum (ER) stress regulates glucose homeostasis and that ER stress preconditioning which induces an adaptive, protective unfolded protein response (UPR) offers cytoprotection against nephrotoxins. Thus the aim of the present study was to use renal proximal tubule cells (PTCs) to further elucidate the link between the BSA-induced ER stress and alpha-methyl-d-glucopyranoside (alpha-MG) uptake and to identify related signaling pathways. Among ER stress inducers such as high glucose, BSA, H2O2, or tumicamycin, BSA pretreatment ameliorated the reduction of Na(+)-glucose cotransporter (SGLT) expression and alpha-MG uptake by gentamicin or cyclosporine A. Immunofluorescence studies revealed that BSA (10 mg/ml) stimulated the expression of glucose-regulated protein 78 (GRP78), an ER stress biomarker. In addition, BSA increased levels of GRP78 protein expression and eukaryotic initiation factor 2alpha (eIF2alpha) phosphorylation in a time-dependent manner. Furthermore, transfection with a GRP78-specific small interfering RNA (siRNA) inhibited BSA-stimulated SGLT expression and alpha-MG uptake. In experiments designed to unravel the mechanisms underlying BSA-induced ER stress, BSA stimulated the production of cellular reactive oxygen species (ROS), and antioxidants such as ascorbic acid or N-acetylcysteine (NAC) blocked BSA-induced increases in GRP78 activation, eIF2alpha phosphorylation, SGLT expression, and alpha-MG uptake. Moreover, the cells upregulated peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA levels in response to BSA or troglitazone (a PPARgamma agonist), but BSA was ineffective in the presence of GW9662 (a PPARgamma antagonist). In addition, both BSA and troglitazone stimulated GRP78 and eIF2alpha activation, SGLT expression, and alpha-MG uptake, whereas GW9662 inhibited the effects of BSA. BSA also stimulated phosphorylation of JNK and NF-kappaB, and GW9662 or GRP78 siRNA attenuated this response. Moreover, SP600125 or SN50 effectively blocked SGLT expression and alpha-MG uptake in BSA- or PPARgamma agonists (troglitazone or PGJ2)-treated PTCs. We conclude that BSA induces ER stress through ROS production and PPARgamma activation, which subsequently activates JNK/NF-kappaB signaling to enhance glucose uptake in renal PTCs.

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Section: Discussionmentioning

confidence: 96%

“…hand precipitating a proapoptotic or inflammatory environment that ultimately leads to tubular atrophy and renal failure (6,8,19,27,43). Proteinuria is a common hallmark of glomerular pathology, and the magnitude of proteinuria is a well-known adverse prognostic factor in a wide variety of kidney diseases.…”

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confidence: 99%

Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Lee¹,

Han²

2009

American Journal of Physiology-Renal Physiology

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“…Albumin-mediated renoprotection may be explained by several mechanisms, including maintaining renal perfusion [6,31,32], promoting proximal tubular integrity and function [22,33-38], binding of endogenous toxins and nephrotoxic drugs [39-42], and preventing oxidative damage and binding and delivering protective lysophosphatidic acid [34,36,43,44]. The important renoprotective role of serum albumin was underscored by a recent meta-analysis showing hypoalbuminemia to be a potent independent risk factor both for AKI and for death following the development of AKI [45].…”

Section: Discussionmentioning

confidence: 99%

Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials

et al. 2010

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IntroductionIt has been hypothesized that hyperoncotic colloids might contribute to acute kidney injury (AKI). However, the validity of this hypothesis remains unclear.MethodsA meta-analysis was conducted of randomized controlled trials evaluating AKI after infusion of hyperoncotic albumin and hydroxyethyl starch (HES) solutions. Mortality was a secondary endpoint. Eligible trials were sought by multiple methods, and the pooled odds ratios (OR) for AKI and death and 95% confidence intervals (CI) were computed under a random effects model.ResultsEleven randomized trials with a total of 1220 patients were included: 7 evaluating hyperoncotic albumin and 4 hyperoncotic HES. Clinical indications were ascites, surgery, sepsis and spontaneous bacterial peritonitis. Hyperoncotic albumin decreased the odds of AKI by 76% (OR, 0.24; CI, 0.12-0.48; P < 0.0001), while hyperoncotic HES increased those odds by 92% (OR, 1.92; CI, 1.31-2.81; P = 0.0008). Parallel effects on mortality were observed, with hyperoncotic albumin reducing the odds of death by 48% (OR, 0.52; CI, 0.28-0.95; P = 0.035) and hyperoncotic HES raising those odds by 41% (OR, 1.41; CI, 1.01-1.96; P = 0.043).ConclusionsThis meta-analysis does not support the hypothesis that hyperoncotic colloid solutions per se injure the kidney. Renal effects appear instead to be colloid-specific, with albumin displaying renoprotection and HES showing nephrotoxicity.

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“…Exposure of renal proximal tubular cell to albumin activates EGFR, leading to nuclear factor-κB activation and cell cycle progression (124). In human renal epithelial cells, albumin activates EGFR and ERK via ROS production and this signaling cascade is required for interleukin-8 induction (125).…”

Section: Kidneymentioning

confidence: 99%

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System

Forrester

Kawai

O’Brien

et al. 2016

Annu. Rev. Pharmacol. Toxicol.

141

123

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Accumulating studies suggest that the epidermal growth factor receptor (EGFR) activation is associated with the physiology and pathophysiology of the cardiovascular system, and inhibition of EGFR activity is emerging as a potential therapeutic strategy to treat diseases, including hypertension, cardiac hypertrophy, renal fibrosis and abdominal aortic aneurysm. The capacity of G protein-coupled receptor (GPCR) agonists, such as angiotensin II (AngII), to promote EGFR signaling is well described – a process termed EGFR “transactivation” – yet delineating the molecular processes and functional relevance of this crosstalk has been challenging. Moreover, these critical findings are dispersed among many different fields. The aim of our review is to highlight the recent advancement of the signaling cascades and downstream consequences of EGFR transactivation within the cardiovascular renal system in vitro and in vivo. We will also focus on linking EGFR transactivation to animal models of the disease as well as the potential therapeutic applications.

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Albumin-stimulated DNA synthesis is mediated by Ca²⁺/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-κB signal pathways in renal proximal tubule cells

Abstract: Lee YJ, Han HJ. Albumin-stimulated DNA synthesis is mediated by Ca 2ϩ /PKC as well as EGF receptor-dependent p44/42 MAPK and NF-B signal pathways in renal proximal tubule cells.

Cited by 23 publications

References 42 publications

Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System

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Albumin-stimulated DNA synthesis is mediated by Ca2+/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-κB signal pathways in renal proximal tubule cells

Abstract: Lee YJ, Han HJ. Albumin-stimulated DNA synthesis is mediated by Ca 2ϩ /PKC as well as EGF receptor-dependent p44/42 MAPK and NF-B signal pathways in renal proximal tubule cells.

Cited by 23 publications

References 42 publications

Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Effect of BSA-induced ER stress on SGLT protein expression levels and α-MG uptake in renal proximal tubule cells

Hyperoncotic colloids and acute kidney injury: a meta-analysis of randomized trials

Epidermal Growth Factor Receptor Transactivation: Mechanisms, Pathophysiology, and Potential Therapies in the Cardiovascular System

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Albumin-stimulated DNA synthesis is mediated by Ca²⁺/PKC as well as EGF receptor-dependent p44/42 MAPK and NF-κB signal pathways in renal proximal tubule cells