title: GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA cascade in colitis.
abstract: Glycinamide ribonucleotide formyltransferase (GART) has been established as a pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in many diseases. We aimed to investigate the role of GART in the pathogenesis of Crohn's disease (CD). In our study, we demonstrated for the first time that GART expression is up-regulated in patients with active CD and in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the inhibition of GART induced cellular apoptosis and suppressed the migration of IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated protein kinase (MAPK) pathway, following with the dys-regulation of p53 and p53 up-regulated modulator of apoptosis (PUMA). Taken together, GART plays a critical role in the protection of cellular apoptosis and migration of intestinal epithelial cells to maintain the integrity of the epithelial barrier, thus providing a new potential approach in designing a novel therapy for CD.
authors.affiliation: Sir Run Run Hospital, Nanjing Medical University, No.109 Longmian Road, Nanjing, Jiangsu, China.
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Bai
authors.affiliation: The First Affiliated Hospital with Nanjing Medical University, No.300, Guangzhou Road, Nanjing, Jiangsu, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Jie
authors.affiliation: The First Affiliated Hospital with Nanjing Medical University, No.300, Guangzhou Road, Nanjing, Jiangsu, China.
authors.forename: Sun
authors.initials: S
authors.lastname: Wei
authors.affiliation: Linyi county people's hospital, Dezhou, Shandong, China.
authors.forename: Shidong
authors.initials: S
authors.lastname: Wang
authors.affiliation: Linyi county people's hospital, Dezhou, Shandong, China.
authors.forename: Huarui
authors.initials: H
authors.lastname: Guo
authors.affiliation: The First Affiliated Hospital with Nanjing Medical University, No.300, Guangzhou Road, Nanjing, Jiangsu, China. tqy831@163.com.
authors.forename: Qiyun
authors.initials: Q
authors.lastname: Tang
mesh_terms: D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D003092:Colitis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004847:Epithelial Cells / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology / Q000201:enzymology; D020935:MAP Kinase Signaling System; D051026:Phosphoribosylglycinamide Formyltransferase / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051026:Phosphoribosylglycinamide Formyltransferase; D048051:p38 Mitogen-Activated Protein Kinases; D019731:Carbon-Nitrogen Ligases; C494823:GART protein, human
keywords: Apoptosis; Crohn’s disease; Glycinamide ribonucleotide formyltransferase; Intestinal epithelial cells; P38; P53