Wogonin protects against cisplatin-induced acute kidney injury by targeting RIPK1-mediated necroptosis

Meng, Xiao‐Ming; Li, Hai-Di; Wang, Weifeng; Tang, Patrick Ming‐Kuen; Ren, Gui-Ling; Gao, Li; Li, Xiaofeng; Yang, Yang; Xu, Tao; Ma, Tran; Zeng, Li; Huang, Cheng; Zhang, Lei; Lv, Xiongwen; Li, Jun

doi:10.1038/labinvest.2017.115

Cited by 70 publications

(55 citation statements)

References 53 publications

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“…PPBICA not only limited programmed cell death induced by TNF-α and TNF-α plus z-VAD, but also prevented cisplatin-induced necroptosis and apoptosis. Our previous study showed that cisplatin induced the activation of caspase3-dependent apoptosis and RIPK-mediated necroptosis of tubular epithelial cells [2,21,22]. This may lead to loss of tubular epithelial cells and tubule integrity, where adherent junctions are further damaged, back-leaking of tubular fluid and inflammatory responses accelerated, which causes renal dysfunction.…”

Section: Discussionmentioning

confidence: 99%

Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute kidney injury by attenuating inflammation and programmed cell death

Gao

Liu

Zang

et al. 2018

Laboratory Investigation

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E-cadherin is a major component of tubular adherent proteins that maintain intercellular contacts and cell polarity in epithelial tissue. It is involved in pathological processes of renal cell carcinoma and fibrotic diseases via epithelial-mesenchymal transition. Although studies have shown E-cadherin is significantly downregulated in acute kidney injury (AKI), its function in AKI is unknown. Here, we evaluated cell damage and inflammation in cisplatin-stimulated tubular epithelial cell lines after disrupting E-cadherin and restoring it with PPBICA, a small molecule identified by high-throughput screening. We also determined the therapeutic potential of restoring E-cadherin in vivo. Results show cisplatin reduced E-cadherin expression both in mouse kidney and proximal tubular epithelial cell lines (mTECs). PPBICA restored E-cadherin levels, which increased cell viability while attenuating programmed cell death. This may be mediated via deactivation of the RIPK1/RIPK3 axis and decreased caspase3 cleavage. In addition, PPBICA suppressed inflammatory response in cisplatin-treated mTECs, which correlated with suppressed NF-κB phosphorylation and promoter activity. In contrast, disruption of E-cadherin promoted cell damage and inflammation. PPBICA failed to further attenuate kidney damage in E-cadherin knockdown cells, indicating that PPBICA protects against mTECs through E-cadherin restoration. We also found that peritoneal injection of PPBICA in mice prevented loss of renal function and tubular damage by suppressing NF-κB-driven renal inflammation and RIPK-regulated programmed cell death. This was driven by restoration of E-cadherin in cisplatin nephropathy. Additionally, PPBICA attenuated cisplatin-induced kidney damage in an established AKI model, indicating its therapeutic potential in the treatment of AKI. In conclusion, E-cadherin plays functional roles in tubule integrity, programmed cell death, and renal inflammation. Our results underscore the potential of E-cadherin restoration as a novel therapeutic strategy for AKI.

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Section: Discussionmentioning

confidence: 99%

Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute kidney injury by attenuating inflammation and programmed cell death

Gao

Liu

Zang

et al. 2018

Laboratory Investigation

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“…Accordingly, phenytoin attenuated post-ischemic AKI in mice [15]. Wogonin displayed similar efficacy on RIPK1 modulation in vitro and attenuated cisplatin-induced AKI in mice [16]. These data consistently suggest that the kinase domain of RIPK1 contributes to various forms of AKI, although the cell type-specific contribution and the window-of-opportunity for intervention have not yet been systematically explored.…”

Section: Essential Proteins Of the Necroptosis Pathway Contributing Tmentioning

confidence: 99%

Necroptosis in Acute Kidney Injury

Anders¹

2018

Nephron

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Background/Aims: Regulated necrosis is an expanding research field with important implications for acute kidney injury (AKI). A focused review of the evolving evidence for necroptosis in AKI, one of several forms of regulated necrosis defines the known and unknown. Methods: A literature search was performed in PUBMED and ScienceDirect between January 1957 and April 2018 using the following keywords: “acute kidney injury,” “necrosis,” “necroptosis,” “necroinflammation.” Results: The necroptosis signaling cascade involves a number of proteins including receptor-interacting protein-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like pseudokinase (MLKL) as well as the MLKL regulator RGMb. The existing experimental evidence in AKI based on mice with genetic deletions of these proteins, more or less specific inhibitory compounds, and diverse experimental AKI models is reviewed. Conclusion: There is broad consistency suggesting a role for necroptosis in AKI, but some studies report divergent evidence potentially relating to the specific model used and the time point of analysis. Mlkl-deficient mice are currently the most specific and reliable experimental tool to study necroptosis in vivo (in kidney disease). The clinical potential of necroptosis inhibition in AKI is to be evaluated, but conceptual problems in AKI definitions and in complex clinical scenarios remain a concern.

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“…Cisplatin-induced AKI is closely related to the activity of lipid peroxidation and oxidative defense in the kidney. It has been found that the response of many cells to oxidative stress involves signaling proteins which act through the antioxidant response element (ARE) and the transcription factor erythrocyte 2-associated factor 2 (Nrf2) [9], which plays an important role in the regulation of the phase II gene. Nrf2induced heme oxygenase-1 (HO-1) prevents cytotoxicity of various oxidative stress and inflammatory responses [10].…”

Section: Introductionmentioning

confidence: 99%

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

Deng

Jiang

Chen

et al. 2020

Oxidative Medicine and Cellular Longevity

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Acute kidney injury (AKI) is a common clinical problem, characterized by a sudden loss of renal function, a high risk of death, and the eventual development of renal fibrosis and renal failure. Cordyceps cicadae is a traditional Chinese medicine with the potential function of kidney protection. We analyze two sputum extracts, a water extract (WCC), and an ethanol extract (ECC), to assess the potential of treating AKI in an animal model of kidney injury induced by cisplatin. A nephrotoxic mouse model was first established by intraperitoneal injection of cisplatin. Subsequently, WCC and ECC were orally administered in these mice. The results show that WCC and ECC significantly alleviated cisplatin-induced AKI renal histological changes, serum creatinine (CRE) and blood urea nitrogen (BUN) production, and the levels of NO, TNF-α, IL-1β, and IL-6. The levels of malondialdehyde (MDA) and glutathione (GSH) were suppressed by administration of WCC and ECC. However, WCC treatment prevented these changes significantly better than ECC treatment. In addition, Western blot data showed that WCC attenuated the cisplatin-induced protein expression of cyclooxygenase-2 (COX-2) and inducible NO synthase (iNOS), as well as inhibiting nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) activation in the kidney tissues. Furthermore, WCC greatly inhibited the expression of Toll-like receptor 4 (TLR4) and cisplatin-induced NF-κB activation, as well as dramatically increasing the production of antioxidative enzymes (i.e., superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase, nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase 1 (HO-1)), silent information regulator T1 (Sirt1), and p-AMP-activated protein kinase (AMPK) in the kidney tissues. In addition, we found that WCC increased the expression levels of the autophagy-related proteins LC3B and Beclin-1; proapoptotic proteins, including cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP) 1; and organic anion transporters 1 (OAT1) and 3 (OAT3) in the kidney tissues. Finally, WCC, ECC, and two bioactive compounds—adenosine and N6-(2-hydroxyethyl) adenosine (HEA)—inhibited the production of nitrite oxide (NO) and intracellular reactive oxygen species (ROS) triggered by lipopolysaccharide- (LPS-) stimulated RAW264.7 macrophages in vitro. Collectively, WCC could provide a potential therapeutic candidate for the prevention of cisplatin-induced kidney injury through the inhibition of oxidative stress and inflammation.

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Wogonin protects against cisplatin-induced acute kidney injury by targeting RIPK1-mediated necroptosis

Cited by 70 publications

References 53 publications

Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute kidney injury by attenuating inflammation and programmed cell death

Restoration of E-cadherin by PPBICA protects against cisplatin-induced acute kidney injury by attenuating inflammation and programmed cell death

Necroptosis in Acute Kidney Injury

Cordyceps cicadae Mycelia Ameliorate Cisplatin-Induced Acute Kidney Injury by Suppressing the TLR4/NF-κB/MAPK and Activating the HO-1/Nrf2 and Sirt-1/AMPK Pathways in Mice

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