Interleukin-17A induces renal fibrosis through the ERK and Smad signaling pathways

Weng, Cheng‐Hao; Li, Yi-Jung; Wu, Hsin-Hsu; Liu, Shou-Hsuan; Hsu, Hsiang-Hao; Chen, Yung‐Chang; Yang, Chunfeng; Chu, Pao-Hsien; Tian, Ya‐Chung

doi:10.1016/j.biopha.2019.109741

Cited by 34 publications

(20 citation statements)

References 50 publications

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“…Several other ADAM10 substrates are reportedly involved in fibrosis, such as ERK and ephrin‐B2 [30,41]. Ephrin‐B2 expression was too low to detect (data not shown) and the phosphorylation level of Erk was not affected in E18.5 kidneys (supplementary material, Figure S6A), suggesting that ADAM10 specifically regulated Notch activity in our mouse model.…”

Section: Resultsmentioning

confidence: 82%

ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling

Zhu

Dong

et al. 2020

The Journal of Pathology

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Disturbed intrauterine development increases the risk of renal disease. Various studies have reported that Notch signalling plays a significant role in kidney development and kidney diseases. A disintegrin and metalloproteinase domain 10 (ADAM10), an upstream protease of the Notch pathway, is also reportedly involved in renal fibrosis. However, how ADAM10 interacts with the Notch pathway and causes renal fibrosis is not fully understood. In this study, using a prenatal chlorpyrifos (CPF) exposure mouse model, we investigated the role of the ADAM10/Notch axis in kidney development and fibrosis. We found that prenatal CPF-exposure mice presented overexpression of Adam10, Notch1 and Notch2, and led to premature depletion of Six2 + nephron progenitors and ectopic formation of proximal tubules (PTs) in the embryonic kidney. These abnormal phenotypic changes persisted in mature kidneys due to the continuous activation of ADAM10/Notch and showed aggravated renal fibrosis in adults. Finally, both ADAM10 and NOTCH2 expression were positively correlated with the degree of renal interstitial fibrosis in IgA nephropathy patients, and increased ADAM10 expression was negatively correlated with decreased kidney function evaluated by serum creatinine, cystatin C, and estimated glomerular filtration rate. Regression analysis also indicated that ADAM10 expression was an independent risk factor for fibrosis in IgAN.

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Section: Resultsmentioning

confidence: 82%

ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling

Zhu

Dong

et al. 2020

The Journal of Pathology

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“…This effect of IL-17 could in part contribute to the mechanism growth promotion and survival in these leukemia cells. Stimulation of smad3/4 transcriptional factors of the TGF-beta signaling pathway [102,115] by IL-17 may point to potential cross talk between IL-17 and TGF-beta-induced signaling pathways to synergize their biological effects [127,128]. The lack of activation of NF-kB by IL-17 in these leukemia cells is not surprising since typically these leukemia cells constitutively express high levels of active NF-kB, which could explain the apparent lack of NF-kB response to IL-17.…”

Section: Discussionmentioning

confidence: 99%

“…IL-17 signaling pathways are implicated in human diseases including inflammation and cancer [100]. Furthermore, TRAF and TGF-beta-1/smad2/3 signaling pathways are activated by IL-17 [99][100][101][102]. Most of the biological effects of IL-17 were initially observed in different variety of cells but to lesser extent in leukemia cells.…”

Section: Introductionmentioning

confidence: 99%

IL-17 Biological Effects and Signaling Mechanisms in Human Leukemia U937 Cells

Adunyah¹,

Akomeah²,

Arthur³

et al. 2021

Interleukins - The Immune and Non-Immune Systems’ Related Cytokines

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Human Interlekin-17 is produced by memory activated CD4+ T cells and other cells. It was initially considered unique in that its specific receptor is distinct from other cytokine receptors. IL-17 receptor is ubiquitously expressed by different cells including T cells. IL-17 plays a role in regulating growth, immune response and pro-inflammatory responses. It regulates differentiation of a subset of Th0 cells into Th-17 cells, which produce IL-17-induced cytokines. The IL-17R belongs to type 1 cytokine receptors. IL-17 belongs to a superfamily of its own, which includes IL-17A, IL-17B, IL-17C, IL-17E and IL-17F. These members of IL-17 superfamily have some sequence homology but bind to different receptors. Prior to this investigation, limited information existed on the effects of IL-17A in human leukemia cell lines. Our results show that IL-17A promotes growth, anti-apoptotic effects, chemotaxis, cytokine expression and transcriptional factor activation in leukemia cells. IL-17A activates multiple signaling pathways including PI-3 K, Jak–STAT, Raf-ERK1/2 and SRC kinase pathways, which mediate different biological effects of IL-17A in leukemia cells. Our findings implicate IL-17A in leukemia cell growth and survival, supporting potential leukemia therapy via development of anti-IL-17A drugs. This chapter focuses on IL-17A, herein referred to as IL-17.

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“…Damaged tubules also play an important role in the activation of inflammatory pathways leading to renal fibrosis [124,125], and IL-17 activity may contribute to this effect. In vitro studies of proximal tubule cells demonstrated that IL-17 stimulation increased the expression of profibrotic molecules and the production of IL-6 and IL-8, in part via activation of extracellular signal-regulated kinase 1/2 phosphorylation [50,126]. It is unclear if elevated IL-17 is sufficient to induce elevated blood pressure responses or if it serves to modulate other sodium-retaining factors to effect hypertension.…”

Section: Effects On Epithelial Cellsmentioning

confidence: 99%

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

Basile

Ullah

Collet

et al. 2021

Kidney Res Clin Pract

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As of 2017, the global burden of chronic kidney disease (CKD) was estimated to be approximately 9.1%, indicating that CKD is a significant healthcare concern worldwide. Global age-adjusted mortality rates for patients with CKD have declined in the last 30 years, and quality of life metrics decrease as glomerular filtration rate declines [1]. In the period between1990 and 2017, there was an approximate 41% increase in the number of patients with end-stage renal disease (ESRD). Despite this, CKD patients are more likely to die due to complications such as hypertension, cardiovascular disease, anemia, and bone and mineral Both acute and chronic kidney disease have a strong underlying inflammatory component. This review focuses primarily on T helper 17 (Th17) cells as mediators of inflammation and their potential to modulate acute and chronic kidney disease. We provide updated information on factors and signaling pathways that promote Th17 cell differentiation with specific reference to kidney disease. We highlight numerous clinical studies that have investigated Th17 cells in the setting of human kidney disease and provide updated summaries from various experimental animal models of kidney disease indicating an important role for Th17 cells in renal fibrosis and hypertension. We focus on the pleiotropic effects of Th17 cells in different renal cell types as potentially relevant to the pathogenesis of kidney disease. Finally, we highlight studies that present contrasting roles for Th17 cells in kidney disease progression.

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Interleukin-17A induces renal fibrosis through the ERK and Smad signaling pathways

Cited by 34 publications

References 50 publications

ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling

ADAM10 mediates ectopic proximal tubule development and renal fibrosis through Notch signalling

IL-17 Biological Effects and Signaling Mechanisms in Human Leukemia U937 Cells

T helper 17 cells in the pathophysiology of acute and chronic kidney disease

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