title: Up regulation of glyoxylate reductase/hydroxypyruvate reductase (GRHPR) is associated with intestinal epithelial cells apoptosis in TNBS-induced experimental colitis.
abstract: 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.
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zong
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Hygiene, Nantong University, Nantong, Jiangsu, China.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Nie
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong, Jiangsu, China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: Ji
authors.affiliation: Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong, Jiangsu, China.
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Dawei
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Gong
authors.affiliation: Department of Pathology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gastroenterology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China; Department of Nutrition and Food Hygiene, School of Public Hygiene, Nantong University, Nantong, Jiangsu, China; Jiangsu Province Key Laboratory for Inflammation and Molecular Drug Target, Nantong, Jiangsu, China; Department of Pathology, Affiliated Hospital of Nantong University, Medical College of Nantong University, Nantong, Jiangsu, China. Electronic address: zcy603877@163.com.
authors.forename: Guoxiong
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D003092:Colitis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007422:Intestines / Q000473:pathology; D051379:Mice; D014302:Trinitrobenzenesulfonic Acid; D015854:Up-Regulation
chemical_list: D014302:Trinitrobenzenesulfonic Acid; D000429:Alcohol Oxidoreductases; C020830:glyoxylate reductase; D053148:Caspase 3
keywords: Apoptosis; Crohn's disease; Glyoxylate reductase/hydroxypyruvate reductase; Intestinal epithelial cells