Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

Huang, Jau‐Shyang; Guh, Jinn‐Yuh; Hung, Wen‐Chun; Yang, Mei‐Li; Lai, Yung‐Hsiung; Chen, Hung‐Chun; Chuang, Li‐Yeh

doi:10.1042/bj3420231

Cited by 55 publications

(9 citation statements)

References 48 publications

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“…Briefly, a 30 mg sample of cell lysate was subjected to electrophoresis on 12% sodium dodecyl sulfate-polyacrylamide gels. 39 The samples were then electroblotted on polyvinylidene difluoride membranes. After blocking, blots were incubated with antibody in blocking solution for 1 h followed by two 5-min washes in phosphatebuffered saline containing 0.1% Tween 20.…”

Section: Immunoblottingmentioning

confidence: 99%

“…Briefly, 8 Â 10 6 cells were harvested and suspended in hypotonic buffer A (10 mM HEPES, pH 7.6, 10 mM KCl, 1 mM DTT, 0.1 mM EDTA, and 0.5 mM phenylmethylsulfonyl fluoride) for 10 min on ice and vortexed for 10 s. 39 Nuclei were pelleted by centrifugation at 12 000 g for 5 min. The supernatants containing cytosolic proteins were collected.…”

Section: Preparation Of Nuclear Extractsmentioning

confidence: 99%

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Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells

Chuang

Guh

Chiou

et al. 2007

Kidney International

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Transforming growth factor-beta (TGF-beta), Smads, and the cyclin-dependent kinase (cdk) inhibitor p21(WAF1) are important in the pathogenesis of diabetic tubular hypertrophy. Phosphoinositide 3 kinase (PI3K)/Akt kinase activity is increased in diabetic glomerular hypertrophy. Thus, we studied the role of PI3K in high glucose (30 mM)-induced p21(WAF1), Smad2/3, and cell cycle-dependent hypertrophy in LLC-PK1 cells. We found that high glucose time-dependently (1-48 h) increased PI3K/Akt kinase activity. LY294002 (a PI3K inhibitor) attenuated high glucose-induced cell cycle-dependent (G(0)/G(1) phase) hypertrophy at 72 h while attenuating high glucose-induced p21(WAF1) gene transcription and protein expression at 36-48 h. LY294002 also attenuated high glucose-induced binding of p21(WAF1) to the cyclin E/cdk2 complex, whereas attenuating high glucose-induced TGF-beta bioactivity, Smad2/3 phosphorylation, and Smad2/3 DNA-binding activity at 36-48 h. We concluded that PI3K is required for high glucose-induced cell cycle-dependent hypertrophy, p21(WAF1) transcription and expression, p21(WAF1) binding to the cyclin E/cdk2 complex, TGF-beta bioactivity, and Smad2/3 activity in LLC-PK1 cells.

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Section: Immunoblottingmentioning

confidence: 99%

Section: Preparation Of Nuclear Extractsmentioning

confidence: 99%

Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells

Chuang

Guh

Chiou

et al. 2007

Kidney International

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“…The activated JAK2 tyrosine-phosphorylate and the latent cytoplasmic STAT3 are involved in AGE-induced cell damage (35). In the present study, it was found that the activation of JAK2 and STAT3 were associated with the AGEs.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of physiological testosterone on advanced glycation end product-induced injury in human endothelial cells

Xie¹,

et al. 2017

Molecular Medicine Reports

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The effect of testosterone, a sex steroid, on endothelial cells is controversial as it is uncertain if it has a protective effect on them. Whether physiological testosterone can inhibit the deleterious effects of advanced glycation end products (AGEs) on endothelial cells remains to be elucidated. The present study focused on elucidating the effect of testosterone on the injury of endothelial cells induced by AGEs. Human umbilical vein endothelial cells (HUVECs) were cultured in vitro and treated with AGEs in the presence or absence of various concentrations of testosterone. The cell viability in each group was measured using an MTS assay. Early-stage apoptosis was detected using flow cytometry with Annexin V-fluorescein isothiocyanate/propidium iodide double staining, and the expression levels of apoptosis-associated proteins, B cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax) and caspase-3, were determined using western blot analysis. Oxidative stress and pro-inflammatory parameters in the medium were evaluated using an enzyme-linked immunosorbent assay. The MTS results showed that AGEs significantly decreased the proliferation of HUVECs, whereas a physiological concentration of testosterone alleviated this damage. Physiological concentrations of testosterone protected the HUVECs from AGE-induced apoptosis, mediated by caspase-3 and Bax/Bcl-2. In addition, treatment of the HUVECs with AGEs caused a significant decrease in anti-oxidative parameters, but increased the concentrations of malondialdehyde and tumor necrosis factor-α. The activation of Janus kinase 2 and signal transducer and activator of transcription 3 was significantly increased by incubation with AGEs. However, pre-incubation with a physiological concentration of testosterone attenuated these changes. Therefore, the data obtained in the present study established the potential role of physiological testosterone in ameliorating AGE-induced damage in HUVECs.

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“…Using the UUO model, we then found that, during the fibrotic process, patchy promotion of tubular epithelial proliferation and survival, and interstitial cell apoptosis were linked spatially and temporally with increased pERK expression (12). There is evidence of an interactive mechanistic pathway between the MAPK signalling pathway and JAK/STAT signalling (18,19), and for a role for the JAK/ STAT pathway in kidney fibrosis (3)(4)(5)(6). In this study, where we investigated mRNA for JAK1, JAK2 and JAK3, only JAK3 mRNA had any marked change using the established in vitro model with cells central to development of fibrosis (tubular epithelium and renal fibroblasts).…”

Section: Discussionmentioning

confidence: 99%

“…Alterations in the JAK/STAT signalling pathway may mediate signalling initiated by reactive oxygen species, as well as other pro-fibrotic factors such as cytokines, growth factors and angiotensin II (3,4). Renal fibroblast (NRK49F) proliferation induced by advanced glycation endproducts (AGE), often formed after oxidative stress, occurred through a JAK/STAT-dependent pathway (3,5,6), but only in association with JAK2 activation and not any of the other members of the JAK family (JAK1, JAK3 or TYK2). Koike et al (4) reported that JAK/STAT activation had a protective role against kidney fibrosis in the unilateral ureteral obstruction (UUO) model of kidney fibrosis in mice; but, Pang et al (7) found that use of a STAT3 inhibitor attenuated kidney tubulointerstitial fibrosis in the same rodent model.…”

Section: Introductionmentioning

confidence: 99%

Role of JAK3 in the Pathogenesis of Oxidative Stress-Induced Kidney Fibrosis

Pat

Johnson

Gobé

2018

jrenhep

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The Janus kinase (JAK) tyrosine kinase family and JAK/STAT signal transduction pathway may act in kidney fibrogenesis. JAK3 expression was investigated in in vitro and in vivo models of kidney fibrosis involving oxidative stress. There was a marked down-regulation of JAK3 mRNA in rat kidney tubular epithelial cells (NRK52E) and fibroblasts (NRK49F) exposed to 1.0 mM H 2 O 2 for 18-20 h compared with controls, which correlated with increased apoptosis and decreased mitosis in both cell lines. However, JAK3 protein levels were not significantly different in control and H2O2-treated epithelial and fibroblast cultures. JAK3 activation (phospho-tyrosine) increased in NRK52E cells and decreased in NRK49F cells with oxidative stress. STAT3 phosphorylation decreased in both cell lines with oxidative stress compared with controls. JAK3 protein expression and localisation were investigated in kidneys using the unilateral ureteral obstruction (UUO) model (0-7 days, rats) of kidney fibrosis that involves oxidative stress. JAK3 protein expression did not differ between UUO and controls; however, JAK3 localisation increased temporally with UUO, with strong epithelial expression in mitotic cells compared with controls. Apoptotic tubular epithelium showed minimal JAK3. In summary, in vitro, decreased kidney JAK3 mRNA after oxidative stress was not seen translationally. Differences in the activation of the JAK3/STAT3 pathway may have different consequences for renal fibrosis. In vivo, changes in JAK3 protein localisation, and especially its co-localisation with mitotic cells, indicate that JAK3 protein may contribute to renal tubular epithelial cell proliferation after oxidative stress.

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Role of the Janus kinase (JAK)/signal transducters and activators of transcription (STAT) cascade in advanced glycation end-product-induced cellular mitogenesis in NRK-49F cells

Cited by 55 publications

References 48 publications

Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells

Phosphoinositide 3-kinase is required for high glucose-induced hypertrophy and p21WAF1 expression in LLC-PK1 cells

Protective effects of physiological testosterone on advanced glycation end product-induced injury in human endothelial cells

Role of JAK3 in the Pathogenesis of Oxidative Stress-Induced Kidney Fibrosis

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