Up regulation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is associated with intestinal epithelial cells apoptosis in TNBS-induced experimental colitis
Copyright © 2016. Published by Elsevier GmbH..
Glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which exists mainly in the liver, is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the formation of primary hyperoxaluria type 2 (PH2). Here, we investigated GRHPR expression and its potential role in both human Crohn's disease (CD) and experimental colitis. Murine experimental colitis models were established by administration of trinitrobenzenesulphonic acid (TNBS). As shown by Western blot, significant up-regulation of GRHPR was found in TNBS-treated mice as compared with normal controls. Immunohistochemistry (IHC) also showed increased GRHPR expression, and the molecule was located in intestinal epithelial cells (IECs). This phenomenon also occurred in patients with Crohn's disease. Besides, in an in vitro study, human IEC line HT-29 cells cultured with tumor necrosis factor α (TNF-α) were used to evaluate the changes in expression of GRHPR. Moreover, overexpression of GRHPR was accompanied by active caspase-3 and cleaved poly ADP-ribose polymerase (PARP) accumulation. Furthermore, knock-down GRHPR could inhibit the accumulation of active caspase-3 and cleaved PARP as shown by Western blot in TNF-α treated HT-29 cells. Flow cytometry assay indicated that interference of GRHPR led to increasing apoptosis of IECs. These data suggested that GRHPR might exert its pro-apoptosis function in IECs. Thus, GRHPR might play an important role in regulating IECs apoptosis, and might be a potential therapeutic target for CD.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:212 |
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| Enthalten in: |
Pathology, research and practice - 212(2016), 5 vom: 14. Mai, Seite 365-71 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Zong, Chunyan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.03.2017 Date Revised 02.12.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.prp.2015.09.019 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM258618604 |
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| 100 | 1 | |a Zong, Chunyan |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Up regulation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is associated with intestinal epithelial cells apoptosis in TNBS-induced experimental colitis |
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| 520 | |a Glyoxylate reductase/hydroxypyruvate reductase (GRHPR), which exists mainly in the liver, is a D-2-hydroxy-acid dehydrogenase that plays a critical role in the formation of primary hyperoxaluria type 2 (PH2). Here, we investigated GRHPR expression and its potential role in both human Crohn's disease (CD) and experimental colitis. Murine experimental colitis models were established by administration of trinitrobenzenesulphonic acid (TNBS). As shown by Western blot, significant up-regulation of GRHPR was found in TNBS-treated mice as compared with normal controls. Immunohistochemistry (IHC) also showed increased GRHPR expression, and the molecule was located in intestinal epithelial cells (IECs). This phenomenon also occurred in patients with Crohn's disease. Besides, in an in vitro study, human IEC line HT-29 cells cultured with tumor necrosis factor α (TNF-α) were used to evaluate the changes in expression of GRHPR. Moreover, overexpression of GRHPR was accompanied by active caspase-3 and cleaved poly ADP-ribose polymerase (PARP) accumulation. Furthermore, knock-down GRHPR could inhibit the accumulation of active caspase-3 and cleaved PARP as shown by Western blot in TNF-α treated HT-29 cells. Flow cytometry assay indicated that interference of GRHPR led to increasing apoptosis of IECs. These data suggested that GRHPR might exert its pro-apoptosis function in IECs. Thus, GRHPR might play an important role in regulating IECs apoptosis, and might be a potential therapeutic target for CD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Apoptosis | |
| 650 | 4 | |a Crohn's disease | |
| 650 | 4 | |a Glyoxylate reductase/hydroxypyruvate reductase | |
| 650 | 4 | |a Intestinal epithelial cells | |
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| 700 | 1 | |a Nie, Xiaoke |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Dongmei |e verfasserin |4 aut | |
| 700 | 1 | |a Ji, Qianqian |e verfasserin |4 aut | |
| 700 | 1 | |a Qin, Yongwei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Liang |e verfasserin |4 aut | |
| 700 | 1 | |a Jiang, Dawei |e verfasserin |4 aut | |
| 700 | 1 | |a Gong, Chen |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Yifei |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Guoxiong |e verfasserin |4 aut | |
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