Protective efficacy of Schizandrin B on ameliorating nephrolithiasis via regulating GSK3β/Nrf2 signaling-mediated ferroptosis in vivo and in vitro

Dong, Caitao; Song, Chao; He, Ziqi; Song, Qianlin; Song, Tianbao; Liu, Junwei; Xiong, Yunhe; Su, Xiaozhe; Yang, Sixing; Liao, Wenbiao

doi:10.1016/j.intimp.2023.110042

Cited by 10 publications

(2 citation statements)

References 59 publications

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“…Similarly, Zhao’s study demonstrated that ANKRD1 promoted the formation of CaOx kidney stones by activating ferroptosis [ 48 ]. Moreover, inhibiting ferroptosis by Schizandrin B was reported to alleviate nephrolithiasis via Nrf2 signaling [ 49 ]. However, the comprehensive relationship between ferroptosis and CaOx nephrolithiasis has not been investigated, as well as the role of LAMP2 and MDM4.…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Hou,

Zhong,

et al. 2024

Aging

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Ferroptosis is a specific type of programmed cell death characterized by iron-dependent lipid peroxidation. Understanding the involvement of ferroptosis in calcium oxalate (CaOx) stone formation may reveal potential targets for this condition. The publicly available dataset GSE73680 was used to identify 61 differentially expressed ferroptosis-related genes (DEFERGs) between normal kidney tissues and Randall's plaques (RPs) from patients with nephrolithiasis through employing weighted gene co-expression network analysis (WGCNA). The findings were validated through in vitro and in vivo experiments using CaOx nephrolithiasis rat models induced by 1% ethylene glycol administration and HK-2 cell models treated with 1 mM oxalate. Through WGCNA and the machine learning algorithm, we identified LAMP2 and MDM4 as the hub DEFERGs. Subsequently, nephrolithiasis samples were classified into cluster 1 and cluster 2 based on the expression of the hub DEFERGs. Validation experiments demonstrated decreased expression of LAMP2 and MDM4 in CaOx nephrolithiasis animal models and cells. Treatment with ferrostatin-1 (Fer-1), a ferroptosis inhibitor, partially reversed oxidative stress and lipid peroxidation in CaOx nephrolithiasis models. Moreover, Fer-1 also reversed the expression changes of LAMP2 and MDM4 in CaOx nephrolithiasis models. Our findings suggest that ferroptosis may be involved in the formation of CaOx kidney stones through the regulation of LAMP2 and MDM4.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Hou,

Zhong,

et al. 2024

Aging

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“…NRF2 regulates several genes that are critical; for ferroptosis, including GPX4 ( 105 ). In erastinor oxalate-induced HK-2 cells, schizandrin B modulates the expression of ferroptosis-related proteins and reduces ferroptosis-related cellular Fe 2+ accumulation and lipid peroxidation by facilitating Nrf2 nuclear translocation ( 106 ). Drugs and substances, such as gallic acid ( 107 ), curcumin ( 108 ) and dimethyl fumarate ( 109 ), significantly ameliorate CaOx crystal-induced renal injury via Nrf2 pathway regulation, which involves antioxidant and antiapoptotic effects and the inhibition of autophagy and inflammation to prevent nephrolithiasis.…”

Section: The Various Forms Of Cell Death and Urolithiasismentioning

confidence: 99%

Cell death‑related molecules and targets in the progression of urolithiasis (Review)

Wu,

Xue,

et al. 2024

Int J Mol Med

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Urolithiasis is a high-incidence disease caused by calcium oxalate (mainly), uric acid, calcium phosphate, struvite, apatite, cystine and other stones. The development of kidney stones is closely related to renal tubule cell damage and crystal adhesion and aggregation. Cell death, comprising the core steps of cell damage, can be classified into various types (i.e., apoptosis, ferroptosis, necroptosis and pyroptosis). Different crystal types, concentrations, morphologies and sizes cause tubular cell damage via the regulation of different forms of cell death. Oxidative stress caused by high oxalate or crystal concentrations is considered to be a precursor to a variety of types of cell death. In addition, complex crosstalk exists among numerous signaling pathways and their key molecules in various types of cell death. Urolithiasis is considered a metabolic disorder, and tricarboxylic acid cycle-related molecules, such as citrate and succinate, are closely related to cell death and the inhibition of stone development. However, a literature review of the associations between kidney stone development, metabolism and various types of cell death is currently lacking, at least to the best of our knowledge. Thus, the present review summarizes the major advances in the understanding of regulated cell death and urolithiasis progression.

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FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway

Zhang,

Jiang

et al. 2024

Cytotechnology

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Protective efficacy of Schizandrin B on ameliorating nephrolithiasis via regulating GSK3β/Nrf2 signaling-mediated ferroptosis in vivo and in vitro

Cited by 10 publications

References 59 publications

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Identification and validation of the biomarkers related to ferroptosis in calcium oxalate nephrolithiasis

Cell death‑related molecules and targets in the progression of urolithiasis (Review)

FGF21 relieves calcium oxalate-induced cell injury, apoptosis, oxidative damage and ferroptosis of renal tubular epithelial cells through activating Nrf2 signaling pathway

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