Src Activation of NF-κB Augments IL-1β–Induced Nitric Oxide Production in Mesangial Cells

Jalal, Diane I.; Kone, Bruce C.

doi:10.1681/asn.2005070693

Cited by 21 publications

(9 citation statements)

References 42 publications

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“…This may indicate c-Src regulation of the glomerular function and renal microvasculature. An overexpression of c-Src in murine mesangial cells has been demonstrated to augment NF- κ B activation and nitric oxide production [22]. Furthermore, c-Src activation by in vitro blood-perfused juxtamedullary nephron technique contributed to afferent arteriole constriction induced by angiotensin II [23].…”

Section: Discussionmentioning

confidence: 99%

Rapid Nongenomic Action of Aldosterone on Protein Expressions of Hsp90(αandβ) and pc-Src in Rat Kidney

Eiam-Ong

Sinphitukkul²,

Manotham³

2013

BioMed Research International

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Previous in vitro studies indicated that aldosterone nongenomically phosphorylates epidermal growth factor receptor (EGFR) through activation of upstream signals, heat shock protein 90β (Hsp90β), and cytosolic (c)-Src kinase. We demonstrated that aldosterone rapidly elevates EGFR phosphorylation in rat kidney. There are no in vivo data regarding renal Hsp90(α and β) and phosphorylated (p)c-Src protein expressions. The present study further investigates the expressions of these proteins. Male Wistar rats were intraperitoneally injected with normal saline solution or aldosterone (Aldo: 150 μg/kg BW). After 30 minutes, abundances and localizations of these proteins were determined. Aldosterone enhanced renal Hsp90β protein abundance (P < 0.001), but Hsp90α and pc-Src protein levels remained unaltered. Expression of Hsp90(α and β) was induced prominently in the proximal convoluted tubules (PCTs). Activation of Hsp90α was observed in vascular and outer medulla regions, whereas Hsp90β was induced in the cortex. Immunoreactivity of pc-Src was elevated in PCT with obvious staining at the luminal membrane. This in vivo study is the first to demonstrate that aldosterone nongenomically elevates Hsp90(α and β) protein expressions in rat kidney. Aldosterone had no effect on pc-Src protein levels but modulated localization. These results indicate that aldosterone regulates upstream mediators of EGFR transactivation in vivo.

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Section: Discussionmentioning

confidence: 99%

Rapid Nongenomic Action of Aldosterone on Protein Expressions of Hsp90(αandβ) and pc-Src in Rat Kidney

Eiam-Ong

Sinphitukkul²,

Manotham³

2013

BioMed Research International

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“…Src and Syk kinases in innate cells either initiate or regulate various signaling pathways responding to many stimuli [9]. Activation of Src kinases mediate phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/IκBα/NF-κB signaling, and Src kinase plays an essential role to recruit or activate of immune cells [9,24,30,31,32]. The Src family of kinase inhibitors has been considered as anti-inflammatory reagents, for example, dasatinib is used for treatment of chronic myeloid leukemia [33].…”

Section: Discussionmentioning

confidence: 99%

Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways

Kim

Kang

Lee

et al. 2019

IJMS

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Dehydroabietic acid (DAA) is a naturally occurring diterpene resin acid derived from coniferous plants such as Pinus and Picea. Various bioactive effects of DAA have been studied including antibacterial, antifungal, and anticancer activities. However, the anti-inflammatory mechanism of DAA remains unclear. We evaluated the anti-inflammatory effect of DAA in macrophage cell lines. Dehydroabietic acid clearly reduced nitric oxide (NO) production and inflammatory gene expression decreased according to RT-PCR results. Dehydroabietic acid displayed anti-inflammatory activity at the transcriptional level in results from NF-κB- or AP-1-mediated luciferase assays. To identify the DAA target protein, we investigated NF-κB and AP-1 pathways by Western blotting analysis. Dehydroabietic acid suppressed the activity of proto-oncogene tyrosine protein kinase (Src) and spleen tyrosine kinase (Syk) in the NF-κB cascade and transforming growth factor beta-activated kinase 1 (TAK1) in the AP-1 cascade. Using overexpression strategies, we confirmed that DAA targeted these kinases. Our findings demonstrate the anti-inflammatory effects and molecular mechanism of DAA. This suggests that DAA has potential as a drug or supplement to ameliorate inflammation.

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“…In a separate study, Choudhury et al showed that c-Src can signal to the nucleus to activate CDK2 and then promotes DNA synthesis in mesangial cells in response to platelet-derived growth factor (11). In addition, Jalal and Kone reported that Src mediates activation of NF-B, a critical transcription factor that is involved in GN and inflammatory host responses in mesangial cells (33). Because mesangial cell proliferation is the defining mechanism in mesangial proliferative GN, these results suggest that c-Src is critically involved in the pathogenesis of this disease.…”

Section: Role Of Src Kinase In Glomerulonephritismentioning

confidence: 99%

Src family kinases in chronic kidney disease

Wang

Zhuang

2017

American Journal of Physiology-Renal Physiology

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Src family kinases (SFKs) belong to nonreceptor protein tyrosine kinases and have been implicated in the regulation of numerous cellular processes, including cell proliferation, differentiation, migration and invasion, and angiogenesis. The role and mechanisms of SFKs in tumorgenesis have been extensively investigated, and some SFK inhibitors are currently under clinical trials for tumor treatment. Recent studies have also demonstrated the importance of SFKs in regulating the development of various fibrosis-related chronic diseases (e.g., idiopathic pulmonary fibrosis, liver fibrosis, renal fibrosis, and systemic sclerosis). In this article, we summarize the roles of SFKs in various chronic kidney diseases, including glomerulonephritis, diabetic nephropathy, human immunodeficiency virus-associated nephropathy, autosomal dominant form of polycystic kidney disease, and obesity-associated kidney disease, and discuss the mechanisms involved.

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Src Activation of NF-κB Augments IL-1β–Induced Nitric Oxide Production in Mesangial Cells

Abstract: NF-B is a critical transcription factor that is involved in glomerulonephritis and inflammatory host responses and a critical

Cited by 21 publications

References 42 publications

Rapid Nongenomic Action of Aldosterone on Protein Expressions of Hsp90(αandβ) and pc-Src in Rat Kidney

Rapid Nongenomic Action of Aldosterone on Protein Expressions of Hsp90(αandβ) and pc-Src in Rat Kidney

Dehydroabietic Acid Suppresses Inflammatory Response Via Suppression of Src-, Syk-, and TAK1-Mediated Pathways

Src family kinases in chronic kidney disease

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