Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

Hou, Lili; Yuan, Xin; Le, Guannan; Lin, Ziman; Gan, Fang; Li, Haolei; Huang, Kehe

doi:10.1016/j.fct.2021.112037

Cited by 16 publications

(10 citation statements)

References 46 publications

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“…The phosphorylation expression of AMP-dependent protein kinase (AMPK) is elevated, and the phosphorylation expression of mammalian target of rapamycin (mTOR) is decreased, thereby triggering cell autophagy [39]. This notion was also demonstrated by Hou et al, who found that FB1 was through mTORC1 to mediate autophagy induced nephrotoxicity [74]. The expression level of glucose regulatory protein 78 (Bip), activated transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) was also significantly elevated in HepG2 cells [75].…”

Section: Endoplasmic Reticulum Stressmentioning

confidence: 82%

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

et al. 2021

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Fumonisin B1 (FB1), belonging to the member of fumonisins, is one of the most toxic mycotoxins produced mainly by Fusarium proliferatum and Fusarium verticillioide. FB1 has caused extensive contamination worldwide, mainly in corn, rice, wheat, and their products, while it also poses a health risk and is toxic to animals and human. It has been shown to cause oxidative stress, endoplasmic reticulum stress, cellular autophagy, and apoptosis. This review focuses on the current stage of FB1 contamination, its toxic effects of acute toxicity, immunotoxicity, organ toxicity, and reproductive toxicity on animals and humans. The potential toxic mechanisms of FB1 are discussed. One of the main aims of the work is to provide a reliable reference strategy for understanding the occurrence and toxicity of FB1.

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Section: Endoplasmic Reticulum Stressmentioning

confidence: 82%

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

et al. 2021

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“…8). Although FB1 showed pro-apoptotic effects (Hou et al, 2021), the FB1 concentration used was of low-dose as demonstrated by the weight change and lung histopathology, however, low-dose FB1 only upregulated the pro-apoptosis protein Caspase 9 both in vivo and in vitro, recent researches have proved that Caspase 9 is also attributed to pyroptosis activation (Liu et al, 2022), as our results showed, low-dose FB1 induced signi cant in ammatory response and pyroptosis-related protein expressions in mouse lung and A549. Furthermore, our results showed that apoptosis didn't contribute to the FB1-promoted in ammatory response and injury (Fig.…”

Section: Discussionmentioning

confidence: 93%

Fumonisin B1 aggravates inflammatory injury via mTORC1/pyroptosis, while promotes viral replication via mTORC1/apoptosis in Canine influenza virus-infected mice and A549 cells

Liu

Zhang

et al. 2022

Preprint

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Canine influenza virus (CIV) has spread across the world and been a risk to canine and human. Fumonisin B1 (FB1) is a mycotoxin in feed and food, its pollution is low-level but very common. The co-occurrence of FB1 exposure and CIV infection is unavoidable. Here, we investigated the effects of low-dose FB1 exposure on CIV-induced inflammatory injury, viral replication and the underlying mechanisms in vivo and in vitro. In CIV-infected mice, low-dose FB1 (0.25, 0.5 and 0.75 mg/kg p.i.) treatment promoted systemic and lung inflammatory injury, as demonstrated by increased expressions of pro-inflammatory cytokines in serum and lung, increased occurrence of hemophagocytosis in spleen, promoted macrophage aggregation in lung, aggravated barrier damage and pathological injury of lung. In CIV-infected pulmonary epithelial model A549 cells, low-dose FB1 treatment significantly promoted the increase in pro-inflammatory cytokines expressions and the decrease in tight junction proteins expressions. Meanwhile, FB1 treatment promoted viral replication in mice and A549. Importantly, FB1 promoted CIV-inhibited mTOR/P70S6K signaling pathway and CIV-induced NLRP3-dependent pyroptosis, and inhibited CIV-induced apoptosis. Furthermore, mTORC1 inhibitor rapamycin blocked FB1-promoted pyroptosis, promoted FB1-inhibited apoptosis, and reversed FB1-promoted inflammatory injury and viral replication. NLRP3 inhibitor MCC950 attenuated FB1-aggravated inflammatory injury rather than viral replication, and apoptosis activator LY294002 reversed FB1-promoted viral replication rather than inflammatory injury. Summarily, low-dose FB1 exposure aggravated CIV-induced inflammatory injury and viral replication in vivo and in vitro via mTORC1-triggered apoptosis-pyroptosis shift. Our study provided new sights into the influence of mycotoxin on the virus-host interaction and the CIV control.

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“…Moreover, it has been shown that inhibition of GPX4 induced by Erastin accelerates fibroblast‐to‐myofibroblast differentiation (Gong et al, 2019). Hou et al (2021) further confirm that reduction of GPX4 induced by FB1 facilitates the expression of kidney fibrosis‐related genes and proteins such as collagen I, α‐SMA, and TGF‐β1. Therefore, the above findings reinforce the conclusion that the disruption of GPX4 is involved in the development of kidney fibrosis by modulation of the NF‐κB/inflammation signaling pathway (Figure 4).…”

Section: The Underlying Pathways Of Gpx4 In Fibrotic Diseasementioning

confidence: 86%

Function and regulation of GPX4 in the development and progression of fibrotic disease

Zhao-bing

Zhu

Liu

et al. 2022

Journal Cellular Physiology

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Fibrosis is a common feature of fibrotic diseases that poses a serious threat to global health due to high morbidity and mortality in developing countries. There exist some chemical compounds and biomolecules associated with the development of fibrosis, including cytokines, hormones, and enzymes. Among them, glutathione peroxidase 4 (GPX4), as a selenoprotein antioxidant enzyme, is widely found in the embryo, testis, brain, liver, heart, and photoreceptor cells. Moreover, it is shown that GPX4 elicits diverse biological functions by suppressing phospholipid hydroperoxide at the expense of decreased glutathione (GSH), including loss of neurons, autophagy, cell repair, inflammation, ferroptosis, apoptosis, and oxidative stress. Interestingly, these processes are intimately related to the occurrence of fibrotic disease. Recently, GPX4 has been reported to exhibit a decline in fibrotic disease and inhibit fibrosis, suggesting that alterations of GPX4 can change the course or dictate the outcome of fibrotic disease. In this review, we summarize the role and underlying mechanisms of GPX4 in fibrosis diseases such as lung fibrosis, liver fibrosis, kidney fibrosis, cardiac fibrosis, and myelofibrosis.

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Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

Cited by 16 publications

References 46 publications

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

Research Progress on Fumonisin B1 Contamination and Toxicity: A Review

Fumonisin B1 aggravates inflammatory injury via mTORC1/pyroptosis, while promotes viral replication via mTORC1/apoptosis in Canine influenza virus-infected mice and A549 cells

Function and regulation of GPX4 in the development and progression of fibrotic disease

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