Brain-Derived Neurotrophic Factor Modulates Intestinal Barrier by Inhibiting Intestinal Epithelial Cells Apoptosis in Mice

Zhao, Dongyu; Zhang, W X; Qi, Q-Q; Long, Xin; Li, X; Yu, Y-B; Zuo, Xiuli

doi:10.33549/physiolres.933641

Cited by 17 publications

(12 citation statements)

References 46 publications

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“…In the present study, flow cytometry showed that the number of apoptotic cells increased with increasing OTA concentration (Figure 1), which is consistent with previous studies demonstrating that OTA can induce apoptosis of intestinal cells [20,44,45]. Apoptosis, which is a form of programmed cell death, may disrupt the integrity of the intestinal barrier [46,47]. OTA induces apoptosis by modulating BcL-2 family members [30,48], and activation of MEK/ERK1-2 signaling has been shown to be crucial for OTA-induced apoptosis in HK-2 cells [49].…”

Section: Discussionsupporting

confidence: 92%

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Yang

Gao

Yan

et al. 2019

Toxins

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Ochratoxin A (OTA), an important mycotoxin that occurs in food and animal feed, has aroused widespread concern in recent years. Previous studies have indicated that OTA causes nephrotoxicity, hepatotoxicity, genotoxicity, immunotoxicity, cytotoxicity, and neurotoxicity. The intestinal toxicity of OTA has gradually become a focus of research, but the mechanisms underlying this toxicity have not been described. Here, differentiated Caco-2 cells were incubated for 48 h with different concentrations of OTA and transcriptome analysis was used to estimate damage to the intestinal barrier. Gene expression profiling was used to compare the characteristics of differentially expressed genes (DEGs). There were altogether 10,090 DEGs, mainly clustered into two downregulation patterns. The Search Tool for Retrieval of Interacting Genes (STRING), which was used to analyze the protein–protein interaction network, indicated that 24 key enzymes were mostly responsible for regulating cell apoptosis. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis was used to validate eight genes, three of which were key genes (CASP3, CDC25B, and EGR1). The results indicated that OTA dose-dependently induces apoptosis in differentiated Caco-2 cells. Transcriptome analysis showed that the impairment of intestinal function caused by OTA might be partly attributed to apoptosis, which is probably associated with downregulation of murine double minute 2 (MDM2) expression and upregulation of Noxa and caspase 3 (CASP3) expression. This study has highlighted the intestinal toxicity of OTA and provided a genome-wide view of biological responses, which provides a theoretical basis for enterotoxicity and should be useful in establishing a maximum residue limit for OTA.

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Section: Discussionsupporting

confidence: 92%

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Yang

Gao

Yan

et al. 2019

Toxins

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“…Collectively, these results suggest a crucial role of BDNF in cerebral ischemia. Recent findings in mouse models showed that BDNF inhibited intestinal epithelial cell apoptosis, 16 while NDRG4 deletion decreased BDNF expression 17 …”

Section: Introductionmentioning

confidence: 99%

NDRG4 prevents cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis

Liu

Tong

et al. 2019

Genes & Diseases

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Cerebral ischemia is a major cause of mortality and long-term morbidity worldwide. NDRG4 has been shown to protect against cerebral ischemia, although the underlying mechanisms remain largely unclear. Here we found that NDRG4 expression was decreased in the brain tissues of ischemia/reperfusion (IR) rats, indicating increased apoptosis rates among cerebral cells. NDRG4 restoration via an adenovirus significantly attenuated cerebral infarct sizes and impairments in IR rats. Furthermore, adenovirus-mediated NDRG4 inhibited cell apoptosis in the brains of IR rats and regulated the expression of Bcl-2, Bax, caspase-3, and c-Fos. Moreover, we found that NDRG4 increased expression of BDNF, which is strongly related to cerebral ischemia and cellular apoptosis. Altogether, our findings demonstrate that NDRG4 protects cerebral IR injury by inhibiting cell apoptosis and regulates cerebral cell apoptosis by increasing BDNF expression. These results suggest that NDRG4 may be a therapeutic target for IR treatment.

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“…Unlike the detrimental effects of NGF on gut barrier function, BDNF seems to help maintain intestinal epithelial integrity. It has been shown that the BDNF +/mice had lower trans-epithelial resistance, decreased expression of tight junction proteins, such as occludin, zonula occludens-1 (ZO-1), and claudin-1, and increased expression of claudin-2 in the colon,36 suggesting that endogenous BDNF is essential for the maintenance of intestinal mucosa integrity.BDNF treatment in cultured ht-29 cells from the human colon adenocarcinoma cell line induced upregulation of occludin, ZO-1, claudin-1, and downregulation of claudin-2, 37 further suggesting that BDNF modulates intestinal barrier function through regulating the expression of tight junction proteins. Paradoxically, high level of BDNF was found in the colonic mucosa of post-infectious IBS mice, which was associated with decreased occludin, ZO-1, and claudin-1 expression and impaired intestinal barrier function.…”

mentioning

confidence: 99%

Neurotrophic factors in enteric physiology and pathophysiology

Liu

2018

Neurogastroenterology Motil

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Neurotrophic factors are traditionally recognized for their roles in differentiation, growth, and survival of specific neurons in the central and peripheral nervous system. Some neurotrophic factors are essential for the development and migration of the enteric nervous system along the fetal and post-natal gut. Over the last two decades, several non-developmental functions of neurotrophic factors have been characterized. In the adult gastrointestinal tract, neurotrophic factors regulate gut sensation, motility, epithelial barrier function, and protect enteric neurons and glial cells from damaging insults in the microenvironment of the gut. In this issue of Neurogastroenterology and Motility, Fu et al. demonstrate that brain-derived neurotrophic factor plays a role in the pathogenesis of distention-induced abdominal pain in bowel obstruction. In light of this interesting finding, this mini-review highlights some of the recent advances in understanding of the physiological and pathophysiological roles of neurotrophic factors in the adult gut.

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Brain-Derived Neurotrophic Factor Modulates Intestinal Barrier by Inhibiting Intestinal Epithelial Cells Apoptosis in Mice

Cited by 17 publications

References 46 publications

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

Transcriptome Analysis of Ochratoxin A-Induced Apoptosis in Differentiated Caco-2 Cells

NDRG4 prevents cerebral ischemia/reperfusion injury by inhibiting neuronal apoptosis

Neurotrophic factors in enteric physiology and pathophysiology

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