β-1,4-Galactosyltransferase I involved in Schwann cells proliferation and apoptosis induced by tumor necrosis factor-alpha via the activation of MAP kinases signal pathways

Yuan, Qin; Yang, Huiling; Cheng, Chun; Li, Chunmiao; Wu, Xiujie; Huan, Weipeng; Sun, Huiqing; Zhou, Zhengming; Wang, Yingying; Zhao, Yi; Lü, Xiang; Shen, Aiguo

doi:10.1007/s11010-012-1254-6

Cited by 17 publications

(12 citation statements)

References 41 publications

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“…TNF-induced βGalT1 expression has been demonstrated in vitro in astrocytes, Schwann cells and fibroblast-like synoviocytes [10]–[12]. To study the effect of TNF on βGalT1 expression in vivo , we injected CT mice with TNF, isolated ileum mucosa and examined βGalT1 gene expression by qPCR.…”

Section: Resultsmentioning

confidence: 99%

“…Links between tumor necrosis factor (TNF), a very potent proinflammatory molecule and a key signaling component of the immune system [9] and βGalT1 expression are known. First, stimulation of several cell types with TNF in vitro increases βGalT1 expression [10]–[12]. Second, i n vivo , spinal cord contusion injury as well as injection of LPS into the spinal cord induce βGalT1 expression, and it was suggesting that TNF might play a role in regulating βGalT1 expression.…”

Section: Introductionmentioning

confidence: 99%

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Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis

et al. 2013

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Glycosylation is an essential post-translational modification, which determines the function of proteins and important processes such as inflammation. β-1,4-galactosyltransferase I (βGalT1) is a key enzyme involved in the addition of galactose moieties to glycoproteins. Intestinal mucins are glycoproteins that protect the gut barrier against invading pathogens and determine the composition of the intestinal microbiota. Proper glycosylation of mucus is important in this regard. By using ubiquitously expressing βGalT1 transgenic mice, we found that this enzyme led to strong galactosylation of mucus proteins, isolated from the gut of mice. This galactosylation was associated with a drastic change in composition of gut microbiota, as TG mice had a significantly higher Firmicutes to Bacteroidetes ratio. TG mice were strongly protected against TNF-induced systemic inflammation and lethality. Moreover, βGalT1 transgenic mice were protected in a model of DSS-induced colitis, at the level of clinical score, loss of body weight, colon length and gut permeability. These studies put βGalT1 forward as an essential protective player in exacerbated intestinal inflammation. Optimal galactosylation of N-glycans of mucus proteins, determining the bacterial composition of the gut, is a likely mechanism of this function.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis

et al. 2013

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“…Furthermore, B4GALT1 has been strongly linked with multidrug resistance (8,16), tumor sensitivity to cisplatin (17,18) and promotion of cell death signaling pathways (19). Additionally, the gene undergoes promoter methylation in several cancer types and consequent silencing of the gene (13,20,21).…”

Section: Multifaceted Roles Of 5'-regulatory Region Of the Cancer Assmentioning

confidence: 99%

Multifaceted roles of 5′-regulatory region of the cancer associated gene B4GALT1 and its comparison with the gene family

Al‐Obaide

Alobydi²,

Abdel‐Salam

et al. 2015

International Journal of Oncology

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Abstract. β1,4-Galactosylransferases are a family of enzymes encoded by seven B4GALT genes and are involved in the development of anticancer drug resistance and metastasis. Among these genes, the B4GALT1 shows significant variations in the transcript origination sites in different cell types/tissues and encodes an interesting dually partitioning β-1, 4-galactosyltransferase protein. We identified at 5'-end of B4GALT1 a 1.454 kb sequence forming a transcription regulatory region, referred to by us as the TR1-PE1, had all characteristics of a bidirectional promoter directing the transcription of B4GALT1 in a divergent manner along with its long non-coding RNA (lncRNA) antisense counterpart B4GALT1-AS1. The TR1-PE1 showed unique dinucleotide base-stacking energy values specific to transcription factor binding sites (TFBSs), INR and BRE, and harbored CpG Island (CGI) that showed GC skew with potential for R-loop formation at the transcription starting sites (TSSs). The 5'-regulatory axis of B4GALT1 also included five more novel TFBSs for CTCF, GLI1, TCF7L2, GATA3 and SOX5, in addition to unique (TG) 18 repeats in conjunction with 22 nucleotide TG-associated sequence (TGAS). The five lncRNA B4GALT1-AS1 transcripts showed significant complementarity with B4GALT1 mRNA. In contrast, the rest of B4GALT genes showed fewer lncRNAs, and all lacked the (TG) 18 and TGAS. Our results are strongly supported by the FANTOM5 study which showed tissue-specific variations in transcript origination sites for this gene. We suggest that the unique expression patterns for the B4GALT1 in normal and malignant tissues are controlled by a differential usage of 5'-B4GALT1 regulatory units along with a post-transcriptional regulation by the antisense RNA, which in turn govern the cell-matrix interactions, neoplastic progression, anticancer drug sensitivity, and could be utilized in personalized therapy.

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“…Tumor necrosis factor-α (TNFα) is a multipotent inflammatory cytokine that induces a wide variety of responses including apoptosis and proliferation, Yuan et al reported that low concentration of TNFα induced SCs proliferation, while high concentration of TNFα induced SCs apoptosis in vitro [18]. Here, TUNEL assay was used to detect apoptotic cells in the primary SCs treated with high concentration of TNFα (50 ng/ml).…”

Section: Resultsmentioning

confidence: 99%

Krüppel-Like Factor 6 Rendered Rat Schwann Cell More Sensitive to Apoptosis via Upregulating FAS Expression

et al. 2013

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Krüppel-like factor 6 (KLF6) is a tumor suppressor gene and play a role in the regulation of cell proliferation and apoptosis. After the peripheral nerve injury (PNI), the microenvironment created by surrounding Schwann cells (SCs) is a critical determinant of its regenerative potential. In this study, we examined the effects of KLF6 on SCs responses during PNI. Both KLF6 mRNA and protein expression levels were upregulated in the injured sciatic nerve, and immunofluorescence results showed that many KLF6-positive cells simultaneously expressed the SC markers S-100 and p75NTR. The apoptosis inducers TNFα and cisplatin upregulated KLF6 expression in primary cultured SCs and the SC line RSC96. Although KLF6 overexpression exacerbated cisplatin- and TNFα-induced apoptosis, expression levels of the apoptosis regulators Bcl2 and Bax were not significantly affected in either KLF6-overexpressing or KLF6-depleted RSC96 cells. Realtime PCR arrays and qRT-PCR demonstrated that KLF6 overexpression upregulated four pro-apoptotic genes, FAS, TNF, TNFSF12, and PYCARD, and inhibited expression of the anti-apoptotic IL10 gene expression. Further analysis revealed that FAS protein expression was positively correlated with KLF6 expression in SCs. These data suggest that KLF6 upregulation may render SCs more vulnerable to apoptosis after injury via upregulating FAS expression.

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β-1,4-Galactosyltransferase I involved in Schwann cells proliferation and apoptosis induced by tumor necrosis factor-alpha via the activation of MAP kinases signal pathways

Cited by 17 publications

References 41 publications

Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis

Mice Overexpressing β-1,4-Galactosyltransferase I Are Resistant to TNF-Induced Inflammation and DSS-Induced Colitis

Multifaceted roles of 5′-regulatory region of the cancer associated gene B4GALT1 and its comparison with the gene family

Krüppel-Like Factor 6 Rendered Rat Schwann Cell More Sensitive to Apoptosis via Upregulating FAS Expression

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