A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation

Ishibashi, Ryoichi; Takemoto, Minoru; Akimoto, Yoshihiro; Ishikawa, Takahiro; He, Peng; Maezawa, Yoshiro; Sakamoto, Kenichi; Tsurutani, Yuya; Ide, Shintaro; Ide, Kana; Kawamura, Hajime; Kobayashi, Kazuki; Tokuyama, Hirotake; Tryggvason, Karl; Betsholtz, Christer; Yokote, Koutaro

doi:10.1038/srep25955

Cited by 22 publications

(22 citation statements)

References 43 publications

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“…Based on previous findings, we assessed MCD from an immunological perspective. Consistent with other studies [ 16 , 18 ], experimental outcomes such as transient proteinuria and foot process effacement indicated that LPS nephropathy in mice could be an appropriate animal model simulating human MCD.…”

Section: Discussionsupporting

confidence: 88%

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γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway

Chen

Zhang

et al. 2018

BioMed Research International

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Primary nephrotic syndrome (PNS) is a devastating pediatric disorder. However, its mechanism remains unclear. Previous studies detected B7-1 in podocytes; meanwhile, γδT cells play pivotal roles in immune diseases. Therefore, this study aimed to assess whether and how γδT cells impact podocytes via the CD28/B7-1 pathway. WT and TCRδ−/− mice were assessed. LPS was used to induce nephropathy. Total γδT and CD28+γδT cells were quantitated in mouse spleen and kidney samples. B7-1 and phosphor-SRC levels in the kidney were detected as well. In vitro, γδT cells from the mouse spleen were cocultured with mouse podocytes, and apoptosis rate and phosphor-SRC expression in podocytes were assessed. Compared with control mice, WT mice with LPS nephropathy showed increased amounts of γδT cells in the kidney. Kidney injury was alleviated in TCRδ−/− mice. Meanwhile, B7-1 and phosphor-SRC levels were increased in the kidney from WT mice with LPS nephropathy. CD28+γδT cells were decreased, indicating CD28 may play a role in LPS nephropathy. Immunofluorescence colocalization analysis revealed a tight association of γδT cells with B7-1 in the kidney. High B7-1 expression was detected in podocytes treated with LPS. Podocytes cocultured with γδT cells showed higher phosphor-SRC and apoptosis rate than other cell groups. Furthermore, CD28/B7-1 blockage with CTLA4-Ig in vitro relieved podocyte injury. γδT cells exacerbate podocyte injury via CD28/B7-1 signaling, with downstream involvement of phosphor-SRC. The CD28/B7-1 blocker CTLA4-Ig prevented progressive podocyte injury, providing a potential therapeutic tool for PNS.

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Section: Discussionsupporting

confidence: 88%

“…The animals were injected intraperitoneally with either 200 μ g LPS (Sigma, E. coli 0111:B4. 1 mg/ml in sterile LPS-free PBS) sterile LPS-free PBS, in equal volumes of 200 μ l [ 9 , 15 , 16 ]. Twenty-four-hour urine samples were collected after LPS treatment at 0, 1, 2, 3, 4, 5, 6, and 7 days, respectively.…”

Section: Methodsmentioning

confidence: 99%

γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway

Chen

Zhang

et al. 2018

BioMed Research International

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“…In addition, altered secretion of pro-inflammatory factors, including interleukin (IL)-8 and IL-10, is observed during the early stages of DN, and these factors are major contributors to the pathogenesis of DN [31]. Inhibition of podocyte inflammation induced by fructose [32] or lipopolysaccharides [33] appears to be a promising therapeutic strategy for the prevention of podocyte injury [34]. Whether crocin plays a similar role in relieving the oxidative stress and pro-inflammatory response of podocytes during the progression of DN is unclear.…”

Section: Introductionmentioning

confidence: 99%

Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB

Li¹,

Liu²,

Lei³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Diabetic nephropathy (DN) is a microangiopathic disease characterized by excessive urinary albumin excretion, which occurs in 30% of patients with diabetes mellitus. It is the second leading cause of end-stage renal diseases in China. Nuclear factor-kappa B (NF-κB) is reported to be closely correlated with the inflammation underlying diabetes-associated renal damage. Crocin, a plant-derived compound, has antioxidant properties that may inhibit NF-κB. Methods: In the present study, we used a conditionally immortalized mouse podocyte cell line to explore whether crocin could effectively block albuminuria. Cells were incubated with 15 or 25 mM D-glucose to mimic diabetic conditions. The expression of Wilms tumor 1 (WT-1) and synaptopodin was evaluated to identify differentiated podocytes, and the expression of nephrin, podocin, and CD2ap was measured as markers of slit diaphragms, the main structures within the glomerular filtration barrier. Results: The high-glucose conditions led to reduced nephrin, podocin, and CD2ap expression, which was prevented by pretreatment with crocin. The oxidative stress and pro-inflammatory response of podocytes associated with DN induced by high glucose were also reduced by crocin pretreatment. Phosphorylated IκBα (p-IκBα) expression induced by high glucose was also significantly decreased by crocin pretreatment. Moreover, pyrrolidine dithiocarbamate, a NF-κB inhibitor, pyrrolidine dithio carbamate, augmented the protective effects of crocin. Conclusion: Our results demonstrate a protective role of crocin against damage to podocytes and slit diaphragms under high-glucose conditions via inhibition of NF-κB. This study presents a potential therapy for DN and contributes to the understanding of the mechanism underlying DN.

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“…Sema3G is also expressed in podocytes [106]. Ultrastructural analyses have revealed partially aberrant podocyte foot process structures, but not obvious glomerular defects in Sema3G deficient mice.…”

Section: Semaphorins In Diabetic Nephropathymentioning

confidence: 96%

“…On the other hand, Sema3G overexpression has attenuated inflammatory cytokine expression through the inhibition of lipopolysaccharidinduced Toll-like receptor 4 signaling. Therefore, Sema3G can protect podocytes from inflammatory kidney diseases and diabetic nephropathy [106].…”

Section: Semaphorins In Diabetic Nephropathymentioning

confidence: 99%

The Role of Semaphorins in Metabolic Disorders

Zhu

2020

IJMS

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Semaphorins are a family originally identified as axonal guidance molecules. They are also involved in tumor growth, angiogenesis, immune regulation, as well as other biological and pathological processes. Recent studies have shown that semaphorins play a role in metabolic diseases including obesity, adipose inflammation, and diabetic complications, including diabetic retinopathy, diabetic nephropathy, diabetic neuropathy, diabetic wound healing, and diabetic osteoporosis. Evidence provides mechanistic insights regarding the role of semaphorins in metabolic diseases by regulating adipogenesis, hypothalamic melanocortin circuit, immune responses, and angiogenesis. In this review, we summarize recent progress regarding the role of semaphorins in obesity, adipose inflammation, and diabetic complications.

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A novel podocyte gene, semaphorin 3G, protects glomerular podocyte from lipopolysaccharide-induced inflammation

Cited by 22 publications

References 43 publications

γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway

γδT Cells Exacerbate Podocyte Injury via the CD28/B7-1-Phosphor-SRC Kinase Pathway

Crocin Protects Podocytes Against Oxidative Stress and Inflammation Induced by High Glucose Through Inhibition of NF-κB

The Role of Semaphorins in Metabolic Disorders

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