The role of the Janus kinase family/signal transducer and activator of transcription signaling pathway in fibrotic renal disease

Matsui, Futoshi; Meldrum, Kirstan K.

doi:10.1016/j.jss.2012.06.050

Cited by 62 publications

(50 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The STAT signaling pathway has been shown to be an integral part of the responses of the myocardium to various cardiac insults, including myocardial infarction, oxidative damage, myocarditis, hypertrophy and remodeling, in addition to having a prominent role in cardioprotective therapies such as ischemic preconditioning [9]. The STAT pathway also has been documented to take a part in the pathogenesis of liver fibrosis, pulmonary fibrosis and renal fibrosis [10,11,12], as an especially important mechanism for renal fibrosis by which hyperglycemia contributes to renal damage [13]. These results predict that STAT may have a role in the process of myocardial fibrosis induced by HG.…”

Section: Introductionmentioning

confidence: 99%

STAT1/3 and ERK1/2 Synergistically Regulate Cardiac Fibrosis Induced by High Glucose

Dai

Cui

Zhu

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

Background: Hyperglycaemia promotes the proliferation of cardiac fibroblasts (CFs) and collagen synthesis in CFs. However, the molecular mechanism underlying the effects of HG on proliferation and collagen synthesis of CF, is not completely understood. Objectives: The objectives of the present study were to determine whether the STAT proteins has a functional role in high glucose-induced proliferation of CFs and collagen synthesis in vitro and whether the STAT signaling pathway and MAPK signaling pathway have synergetical effects on high glucose-mediated cardiac fibroblasts proliferation and collagen synthesis. Methods: Rat CFs were cultured in Dulbecco's modified Eagle's medium, supplemented with 5.5 or 25 mmol/L D-glucose, in the presence of absence of STAT1 inhibitor Fludarabine, STAT3 inhibitor S31-201 and ERK1/2 inhibitor PD98059. Proliferation were measured by the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay, the production of Type I and III collagen was evaluated using real-time quantitative RT-PCR and ELISA, and the phosphorylation expression of STAT1 and STAT3 were analyzed by Western blot. Results: High glucose treatment promoted the proliferation of cardiac fibroblasts and collagen types I and III synthesis. High glucose treatment induced STAT1 and STAT3 phosphorylation in cardiac fibroblasts, the mode and level of STAT1 and STAT3 phosphorylation were significantly different. Fludarabine and S31-201 could both inhibited high glucose stimulated proliferation of cardiac fibroblasts and collagen types I and III synthesis with different effects. Combination of Fludarabine and PD98059 or combination of S31-201 and PD98059 both exhibited stronger inhibitions on proliferation of cardiac fibroblasts and collagen types I synthesis, but the effects and functional modes are different. Conclusion: Both STAT1 and STAT3 mediate the proliferation of cardiac fibroblasts and collagen synthesis induced by high glucose. STAT1 and STAT3 both have synergetic effects with ERK1/2 on regulating proliferation of cardiac fibroblasts and collagen types I synthesis.

show abstract

Section: Introductionmentioning

confidence: 99%

STAT1/3 and ERK1/2 Synergistically Regulate Cardiac Fibrosis Induced by High Glucose

Dai

Cui

Zhu

et al. 2013

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…In this regard, monocyte chemoattractant protein-1, macrophage colony-stimulating factor-1, TNFa, and certain epidermal growth factor receptor ligands are among the cytokines capable of causing activation of STAT3 (Darnell et al, 1994;Fitzgerald et al, 2008;Yu et al, 2009). Moreover, monocyte chemoattractant protein-1 and TNFa are known to cause changes in podocyte function, leading to increases in albumin permeability of the glomerular filtration barrier (Fornoni et al, 2008;Matsui and Meldrum, 2012).…”

mentioning

confidence: 99%

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

Abkhezr

Dryer

2014

Mol Pharmacol

View full text Add to dashboard Cite

Previous studies have shown that the transcription factor signal transducer and activator of transcription-3 (STAT3) in podocytes plays an important role in progression of HIV nephropathy and in collapsing forms of glomerulonephritis. Here, we have observed that application of 100 nM angiotensin II (Ang II) to cultured podocytes for 6-24 hours causes a marked increase in the phosphorylation of STAT3 on tyrosine Y705 but has no effect on phosphorylation at serine S727. By contrast, Ang II treatment of short periods (20-60 minutes) caused a small but consistent suppression of tyrosine phosphylation of STAT3. A similar biphasic effect was seen after treatment with the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), an agent that causes activation of Ca -calmodulin-dependent protein kinase II. The stimulatory effects of Ang II appear to be mediated by secretion and accumulation of an unknown factor into the surrounding medium, as they are no longer detected when medium is replaced every 2 hours even if Ang II is continuously present. By contrast, the inhibitory effect of Ang II on STAT3 phosphorylation persists with frequent medium changes. Experiments with neutralizing and inhibitory antibodies suggest that the STAT3 stimulatory factor secreted from podocytes is not interleukin-6, but also suggest that this factor exerts its actions through a receptor system that requires glycoprotein 130.

show abstract

“…The STAT signaling pathway constitutes one of the primary regulatory pathways for cytokine expression (32), and STAT signaling has increasingly been implicated in the pathophysiology of renal disease (27). Among the STAT signaling pathways, STAT3 appears to be central and is best correlated with renal disease (27).…”

Section: Discussionmentioning

confidence: 99%

“…Among the STAT signaling pathways, STAT3 appears to be central and is best correlated with renal disease (27). Kuratsune et al (22) have demonstrated STAT3 activation in renal tubular epithelial cells and myofibroblasts in response to obstruction, with peak p-STAT3 expression occurring 7 days after the onset of obstruction.…”

Section: Discussionmentioning

confidence: 99%

IL-18 induces profibrotic renal tubular cell injury via STAT3 activation

Matsui

Rhee

Hile

et al. 2013

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

is an important mediator of obstruction-induced renal fibrosis and renal tubular epithelial cell (TEC) injury. IL-18's proinflammatory properties have been attributed, in part, to NF-B activation and the stimulation of cytokine gene expression; however, STAT3 has increasingly been shown to mediate renal fibrotic injury. We therefore hypothesized that IL-18 mediates profibrotic TEC injury via STAT3 activation. Male C57BL6 wild-type mice and transgenic mice for human IL-18-binding protein were subjected to unilateral ureteral obstruction or sham operation. The kidneys were harvested 1 or 2 wk afterward and analyzed for active STAT3 (p-STAT3) expression (Western blotting, immunohistochemistry) and suppressor of cytokine signaling 3 (SOCS3) expression. In a separate arm, renal tubular cells (HK-2) were directly stimulated with IL-18 for 2 days with or without the STAT3 inhibitor S3I-201 (50 M). Cell lysates were then analyzed for p-STAT3 and SOCS3 expression, profibrotic cellular changes (collagen and ␣-SMA expression), and tubular cell apoptosis. p-STAT3 and SOCS3 expression increased significantly in response to obstruction; however, a significant reduction in p-STAT3 and SOCS3 expression occurred following 1 wk, but not 2 wk, of obstruction in the presence of IL-18 neutralization. In vitro results similarly demonstrate increased p-STAT3, SOCS3, ␣-SMA, and collagen III expression, and increased collagen production and TEC apoptosis in response to IL-18 stimulation, but the response was significantly diminished in the presence of STAT3 inhibition. These results demonstrate that IL-18-induces profibrotic cellular changes and collagen production in TECs via STAT3 activation.interleukin-18; STAT; kidney; fibrosis, ureteral obstruction

show abstract

The role of the Janus kinase family/signal transducer and activator of transcription signaling pathway in fibrotic renal disease

Cited by 62 publications

References 60 publications

STAT1/3 and ERK1/2 Synergistically Regulate Cardiac Fibrosis Induced by High Glucose

STAT1/3 and ERK1/2 Synergistically Regulate Cardiac Fibrosis Induced by High Glucose

RETRACTION: Angiotensin II and Canonical Transient Receptor Potential-6 Activation Stimulate Release of a Signal Transducer and Activator of Transcription 3–Activating Factor from Mouse Podocytes

IL-18 induces profibrotic renal tubular cell injury via STAT3 activation

Contact Info

Product

Resources

About