Heat-shock transcription factor 2 promotes sodium butyrate-induced autophagy by inhibiting mTOR in ulcerative colitis

Zhang, Fengrui; Wang, Wen; Niu, Junkun; Yang, Gang; Luo, Juan; Lan, Danfeng; Wu, Jing; Li, Maojuan; Sun, Yuhao; Wang, Kunhua; Miao, Yi

doi:10.1016/j.yexcr.2020.111820

Cited by 21 publications

(16 citation statements)

References 30 publications

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“…In addition, treatment with rapamycin (a widely used autophagy activator) did not attenuate the pathological damage in the colon; however, HM and/or insulin treatment not only greatly ameliorated colon damage but also inhibited colonic autophagy, suggesting that under inflammatory conditions, overactivation of autophagy is harmful to colon tissues. This finding is consistent with the findings of previous studies[ 40 , 41 ].…”

Section: Discussionsupporting

confidence: 94%

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn’s disease via signaling involving distinct classes of phosphatidylinositol 3-kinases

Wang

Zhao

Zhou

et al. 2020

WJG

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BACKGROUND Autophagy is an evolutionarily conserved biological process in eukaryotic cells that involves lysosomal-mediated degradation and recycling of related cellular components. Recent studies have shown that autophagy plays an important role in the pathogenesis of Crohn’s disease (CD). Herbal cake-partitioned moxibustion (HM) has been historically practiced to treat CD. However, the mechanism by which HM regulates colonic autophagy in CD remains unclear. AIM To observe whether HM can alleviate CD by regulating colonic autophagy and to elucidate the underlying mechanism. METHODS Rats were randomly divided into a normal control (NC) group, a CD group, an HM group, an insulin + CD (I + CD) group, an insulin + HM (I + HM) group, a rapamycin + CD (RA + CD) group, and a rapamycin + HM (RA + HM) group. 2,4,6-trinitrobenzenesulfonic acid was administered to establish a CD model. The morphology of the colonic mucosa was observed by hematoxylin-eosin staining, and the formation of autophagosomes was observed by electron microscopy. The expression of autophagy marker microtubule-associated protein 1 light chain 3 beta (LC3B) was observed by immunofluorescence staining. Insulin and rapamycin were used to inhibit and activate colonic autophagy, respectively. The mRNA expression levels of phosphatidylinositol 3-kinase class I ( PI3KC1 ), Akt1 , LC3B , sequestosome 1 ( p62 ), and mammalian target of rapamycin ( mTOR ) were evaluated by RT-qPCR. The protein expression levels of interleukin 18 (IL-18), tumor necrosis factor-α (TNF-α), nuclear factor κB/p65 (NF-κB p65), LC3B, p62, coiled-coil myosin-like BCL2-interacting protein (Beclin-1), p-mTOR, PI3KC1, class III phosphatidylinositol 3-kinase (PI3KC3/Vps34), and p-Akt were evaluated by Western blot analysis. RESULTS Compared with the NC group, the CD group showed severe damage to colon tissues and higher expression levels of IL-18 and NF-κB p65 in colon tissues ( P < 0.01 for both). Compared with the CD group, the HM group showed significantly lower levels of these proteins ( P IL-18 < 0.01 and P p65 < 0.05). There were no significant differences in the expression of TNF-α protein in colon tissue among the rat groups. Typical autophagic vesicles were found in both the CD and HM groups. The expression of the autophagy proteins LC3B and Beclin-1 was upregulated ( P < 0.01 for both) in the colon tissues of rats in the CD group compared with the NC group, while the protein expression of p62 and p-mTOR was downregulated ( P < 0.01 for both). However, these expression trends were significantly reversed in the HM group compared with the CD group ( P LC3B...

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Section: Discussionsupporting

confidence: 94%

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn’s disease via signaling involving distinct classes of phosphatidylinositol 3-kinases

Wang

Zhao

Zhou

et al. 2020

WJG

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“…The mammalian target of rapamycin is a protein kinase and serves as the central regulator responsible for integrating various cellular signaling cascades, especially those derived from amino acids [ 68 ]. A previous study similarly observed that HS could promote the gene or protein expression of mTOR [ 71 ]. Additionally, it was demonstrated that essential amino acids (Leu, Ile, Thr, Met, Arg, Trp and Lys) and non-essential amino acids (Glu and Gln) have the ability to improve the expression of mTOR [ 72 , 73 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Zhang

Liu

et al. 2021

Animals

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Heat stress (HS) is one of the most serious factors to negatively affect the lactation performance of dairy cows. Bovine mammary epithelial cells are important for lactation. It was demonstrated that HS decreases the lactation performance of dairy cows, partly through altering gene expression within bovine mammary epithelial tissue. However, the cellular metabolism mechanisms under HS remains largely unknown. The objective of this study was to determine whether HS induced changes in intracellular metabolites and gene transcription related to amino acid metabolism, amino acid transportation and the mTOR signaling pathway. Immortalized bovine mammary epithelial cell lines (MAC-T cells, n = 5 replicates/treatment) were incubated for 12 h at 37 °C (Control group) and 42 °C (HS group). Relative to the control group, HS led to a greater mRNA expression of heat shock protein genes HSF1, HSPB8, HSPA5, HSP90AB1 and HSPA1A. Compared with the control group, metabolomics using liquid chromatography tandem–mass spectrometry identified 417 differential metabolites with p < 0.05 and a variable importance in projection (VIP) score >1.0 in the HS group. HS resulted in significant changes to the intracellular amino acid metabolism of glutathione, phenylalanine, tyrosine, tryptophan, valine, leucine, isoleucine, arginine, proline, cysteine, methionine, alanine, aspartate and glutamate. HS led to a greater mRNA expression of the amino acid transporter genes SLC43A1, SLC38A9, SLC36A1, and SLC3A2 but a lower mRNA expression of SLC7A5 and SLC38A2. Additionally, HS influenced the expression of genes associated with the mTOR signaling pathway and significantly upregulated the mRNA expression of mTOR, AKT, RHEB, eIF4E and eEF2K but decreased the mRNA expression of TSC1, TSC2 and eEF2 relative to the control group. Compared with the control group, HS also led to greater mRNA expression of the CSN1S2 gene. Overall, our study indicates that bovine mammary epithelial cells may have the ability to resist HS damage and continue milk protein synthesis partly through enhanced intracellular amino acid absorption and metabolism and by activating the mTOR signaling pathway during HS.

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“…Notably, our GSEA and KEGG results suggested that HSF2 was also involved in many immunity-associated pathways (IL−17 signaling pathway and the adaptive immune system) and various microbial infections (hepatitis B, shigellosis, Yersinia infection, and herpes simplex virus 1 infection) (Figures 5,6). A recently study showed that HSF2 was upregulated in ulcerative colitis and was negatively associated with colon inflammation in mice (Wang W. et al, 2020;Zhang F. et al, 2021). NLRP3 inflammasome activation and IL-1β secretion are greatly enhanced in HSF2−/− DSS model mice (Zhang et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…The HSF family contains five members, including HSF1, HSF2, HSF4, HSF5, and HSFY (Akerfelt et al, 2010;Fujimoto and Nakai, 2010;Gomez-Pastor et al, 2018). Numerous studies have demonstrated that HSF1 is associated with DNA damage repair, reprogrammed metabolism oncogenesis, and metastasis (Mendillo et al, 2012;Dai and Sampson, 2016;Dai, 2018;Wang G. et al, 2020;Puustinen and Sistonen, 2020). Thus, HSF1 is believed to be a potential therapeutic target for anticancer therapy Chen et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

Chen

Fan

Liu

et al. 2022

Front. Mol. Biosci.

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Heat shock factor 2 (HSF2), a transcription factor, plays significant roles in corticogenesis and spermatogenesis by regulating various target genes and signaling pathways. However, its expression, clinical significance and correlation with tumor-infiltrating immune cells across cancers have rarely been explored. In the present study, we comprehensively investigated the expression dysregulation and prognostic significance of HSF2, and the relationship with clinicopathological parameters and immune infiltration across cancers. The mRNA expression status of HSF2 was analyzed by TCGA, GTEx, and CCLE. Kaplan-Meier analysis and Cox regression were applied to explore the prognostic significance of HSF2 in different cancers. The relationship between HSF2 expression and DNA methylation, immune infiltration of different immune cells, immune checkpoints, tumor mutation burden (TMB), and microsatellite instability (MSI) were analyzed using data directly from the TCGA database. HSF2 expression was dysregulated in the human pan-cancer dataset. High expression of HSF2 was associated with poor overall survival (OS) in BRCA, KIRP, LIHC, and MESO but correlated with favorable OS in LAML, KIRC, and PAAD. The results of Cox regression and nomogram analyses revealed that HSF2 was an independent factor for KIRP, ACC, and LIHC prognosis. GO, KEGG, and GSEA results indicated that HSF2 was involved in various oncogenesis- and immunity-related signaling pathways. HSF2 expression was associated with TMB in 9 cancer types and associated with MSI in 5 cancer types, while there was a correlation between HSF2 expression and DNA methylation in 27 types of cancer. Additionally, HSF2 expression was correlated with immune cell infiltration, immune checkpoint genes, and the tumor immune microenvironment in various cancers, indicating that HSF2 could be a potential therapeutic target for immunotherapy. Our findings revealed the important roles of HSF2 across different cancer types.

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Heat-shock transcription factor 2 promotes sodium butyrate-induced autophagy by inhibiting mTOR in ulcerative colitis

Cited by 21 publications

References 30 publications

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn’s disease via signaling involving distinct classes of phosphatidylinositol 3-kinases

Herbal cake-partitioned moxibustion inhibits colonic autophagy in Crohn’s disease via signaling involving distinct classes of phosphatidylinositol 3-kinases

Effect of Heat Stress on Bovine Mammary Cellular Metabolites and Gene Transcription Related to Amino Acid Metabolism, Amino Acid Transportation and Mammalian Target of Rapamycin (mTOR) Signaling

Pan-Cancer Integrated Analysis of HSF2 Expression, Prognostic Value and Potential Implications for Cancer Immunity

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