title: SGK1 inhibits cellular apoptosis and promotes proliferation via the MEK/ERK/p53 pathway in colitis.
abstract: OBJECTIVE
  To investigate the role of serum-and-glucocorticoid-inducible-kinase-1 (SGK1) in colitis and its potential pathological mechanisms.
  
  
  METHODS
  SGK1 expression in mucosal biopsies from patients with active Crohn's disease (CD) and normal controls was detected by immunohistochemistry. We established an acute colitis model in mice induced by 2,4,6-trinitrobenzene sulfonicacid, and demonstrated the presence of colitis using the disease activity index, the histologic activity index and hematoxylin and eosin staining. The cellular events and potential mechanisms were implemented with small interference RNA and an inhibitor of signaling molecule (i.e., U0126) in intestinal epithelial cells (IECs). The interaction between SGK1 and the signaling molecule was assessed by co-immunoprecipitation.
  
  
  RESULTS
  SGK1 expression was significantly increased in the inflamed epithelia of patients with active CD and TNBS-induced colitis model (0.58 ± 0.055 vs 0.85 ± 0.06, P < 0.01). At the cellular level, silencing of SGK1 by small interference RNA (siSGK1) significantly inhibited the phosphorylation of mitogen-activated protein kinase kinase 1 (MEK1) and the downstream molecule extracellular signal regulated protein kinase (ERK) 1/2, which induced the upregulation of p53 and Bcl-2-associated X protein, mediating the subsequent cellular apoptosis and proliferation in IECs. Cells treated with MEK1 inhibitor (i.e., U0126) before siSGK1 transfection showed a reversal of the siSGK1-induced cellular apoptosis.
  
  
  CONCLUSIONS
  Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation.
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Jian-An
authors.initials: JA
authors.lastname: Bai
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Gui-Fang
authors.initials: GF
authors.lastname: Xu
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Yan
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Zeng
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Ji
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Jin-Dao
authors.initials: JD
authors.lastname: Wu
authors.affiliation: Jian-An Bai, Gui-Fang Xu, Li-Jun Yan, Wei-Wen Zeng, Qian-Qian Ji, Jin-Dao Wu, Qi-Yun Tang, Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, Jiangsu Province, China.
authors.forename: Qi-Yun
authors.initials: QY
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000139:chemically induced / Q000201:enzymology* / Q000473:pathology; D003106:Colon / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000473:pathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008807:Mice, Inbred BALB C; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D011817:Rabbits; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D017874:Immediate-Early Proteins; D048369:MAP Kinase Kinase 1; D047428:Protein Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D014302:Trinitrobenzenesulfonic Acid; D014409:Tumor Necrosis Factor-alpha; D016159:Tumor Suppressor Protein p53; D000099184:Serum-Glucocorticoid Regulated Kinases; C495901:TP53 protein, human; C482125:MAP2K1 protein, human
keywords: Apoptosis; Colitis; MEK/ERK; Serum-and-glucocorticoid-inducible-kinase-1; p53