Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells

Zhu, Yaping; Cui, Hongwang; Lv, Jie; Li, Guojun; Li, Xiaoyan; Yang, Feng; Zhong, Liangbao

doi:10.1371/journal.pone.0228385

Cited by 16 publications

(16 citation statements)

References 39 publications

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“…KIRC patients in high-risk group exhibited the upregulated expressions of FASLG and ZBP1 but a downregulated TLR3 expression. The pathway of Fas and Fas Ligand (FasL, FASL, FASLG) can initiate necroptosis upstream of RIPK3 and MLKL in renal tubular epithelial cells [34]. The cell surface FasL induces Fas-mediated killing, while autocrine secretion of soluble FasL can protect RCC cells from cytotoxic lymphocytes killing [35].…”

Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature

Chen¹,

Lin²,

Wu³

et al. 2022

Int. J. Med. Sci.

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Background: Necroptosis, a cell death of caspase-independence, plays a pivotal role in cancer biological regulation. Although necroptosis is closely associated with oncogenesis, cancer metastasis, and immunity, there remains a lack of studies determining the role of necroptosis-related genes (NRGs) in the highly immunogenic cancer type, kidney renal clear cell carcinoma (KIRC). Methods: The information of clinicopathology and transcriptome was extracted from TCGA database. Following the division into the train and test cohorts, a three-NRGs (TLR3, FASLG, ZBP1) risk model was identified in train cohort by LASSO regression. The overall survival (OS) comparison was conducted between different risk groups through Kaplan-Meier analysis, which was further validated in test cohort. The Cox proportional hazards regression model was introduced to assess its impact of clinicopathological factors and risk score on survival. ESTIMATE and CIBERSORT algorithms were introduced to evaluate immune microenvironment, while enrichment analysis was conducted to explore the biological significance. Correlation analysis was applied for the correlation assessment between checkpoint gene expression and risk score, between gene expression and therapeutic response. Gene expressions from TCGA were verified by GEO datasets and immunohistochemistry (IHC) analysis. Results: This NRGs-related signature predicted poorer OS in high-risk group, which was also verified in test cohort. Risk score could also independently predict survival outcome of KIRC. Significant changes were also found in immune microenvironment and checkpoint gene expressions between different risk groups, with immune functional enrichment in high-risk group. Interestingly, therapeutic response was correlated with the expressions of NRGs. The expressions of NRGs from TCGA were consistent with those from GEO datasets and IHC analysis. Conclusion:The NRGs-related signature functions as a novel prognostic predictor of immune microenvironment and therapeutic response in KIRC.

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Section: Discussionmentioning

confidence: 99%

A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature

Chen¹,

Lin²,

Wu³

et al. 2022

Int. J. Med. Sci.

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“…Moreover, RIPK1 and RIPK3 independently influence inflammation without affecting cell death ( 59 ). Earlier studies have shown that RIPK3-related necroptosis is the primary form of renal tubular epithelial cell death in rats with chronic renal injury ( 60 ). The hyperglycemia/AGEs-activated intrarenal RAAS system can increase the levels of renin and angiotensin in renal cells ( 61 , 62 ).…”

Section: Necroptosismentioning

confidence: 99%

Cellular Senescence and Regulated Cell Death of Tubular Epithelial Cells in Diabetic Kidney Disease

Shen

Kai-feng

2022

Front. Endocrinol.

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Cellular senescence is frequently evident at etiologic sites of chronic diseases and involves essentially irreversible arrest of cell proliferation, increased protein production, resistance to apoptosis, and altered metabolic activity. Regulated cell death plays a vital role in shaping fully functional organs during the developmental process, coordinating adaptive or non-adaptive responses, and coping with long-term harmful intracellular or extracellular homeostasis disturbances. In recent years, the concept of ‘diabetic tubulopathy’ has emerged. tubular epithelial cells are particularly susceptible to the derangements of diabetic state because of the virtue of the high energy requirements and reliance on aerobic metabolism render. Hyperglycemia, oxidative stress, persistent chronic inflammation, glucose toxicity, advanced glycation end-products (AGEs) accumulation, lipid metabolism disorders, and lipotoxicity contribute to the cellular senescence and different patterns of regulated cell death (apoptosis, autophagic cell death, necroptosis, pyroptosis, and ferroptosis) in tubular epithelial cells. We now explore the ‘tubulocentric’ view of diabetic kidney disease(DKD). And we summarize recent discoveries regarding the development and regulatory mechanisms of cellular senescence, apoptosis, autophagic cell death, necroptosis, pyroptosis, and ferroptosis in the pathogenesis of DKD. These findings provide new perspectives on the mechanisms of DKD and are useful for designing novel therapeutic approaches for the treatment of DKD.

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“… 2 79 Fas/FasL is well-known to induce RIPK-MLKL-mediated necroptosis as well as caspase-dependent apoptosis. 80 81 82 Milhas et al 83 have shown that D609 treatment enhances ceramide increase, leading caspase-independent cell death in response to FasL under zVAD-fmk-mediated inhibition of caspases in Jurkat cells. However, as the authors did not demonstrate the involvement of RIPK and MLKL activation, it was unclear whether this was necroptosis or not.…”

Section: Signal Transduction Is Regulated By Sms-mediated Ceramide/smmentioning

confidence: 99%

Ceramide/Sphingomyelin Rheostat Regulated by Sphingomyelin Synthases and Chronic Diseases in Murine Models

Taniguchi

Okazaki

2020

J Lipid Atheroscler

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Ceramide and sphingomyelin (SM) are major components of the double membranebound sphingolipids. Ceramide is an essential bioactive lipid involved in numerous cell processes including apoptosis, necrosis, and autophagy-dependent cell death. Inversely, SM regulates opposite cellular processes such as proliferation and migration by changing receptor-mediated signal transduction in the lipid microdomain. SM is generated through a transfer of phosphocholine from phosphatidylcholine to ceramide by SM synthases (SMSs). Research during the past several decades has revealed that the ceramide/SM balance in cellular membranes regulated by SMSs is important to decide the cell fate, survival, and proliferation. In addition, recent experimental studies utilizing SMS knockout mice and murine disease models provide evidence that SMS-regulated ceramide/SM balance is involved in human diseases. Here, we review the basic structural and functional characteristics of SMSs and focus on their cellular functions through the regulation of ceramide/SM balance in membrane microdomains. In addition, we present the pathological or physiological implications of SMSs by analyzing their role in SMS-knockout mice and human disease models. This review finally presents evidence indicating that the regulation of ceramide/SM balance through SMS could be a therapeutic target for human disorders.

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Angiotensin II triggers RIPK3-MLKL-mediated necroptosis by activating the Fas/FasL signaling pathway in renal tubular cells

Abstract: Our earlier studies proved that RIPK3-mediated necroptosis might be an important mode of renal tubular cell death in rats with chronic renal injury and the necroptotic cell death

Cited by 16 publications

References 39 publications

A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature

A Novel Prognostic Predictor of Immune Microenvironment and Therapeutic Response in Kidney Renal Clear Cell Carcinoma based on Necroptosis-related Gene Signature

Cellular Senescence and Regulated Cell Death of Tubular Epithelial Cells in Diabetic Kidney Disease

Ceramide/Sphingomyelin Rheostat Regulated by Sphingomyelin Synthases and Chronic Diseases in Murine Models

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