AIM: 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 coimmunoprecipitation.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(si SGK1) 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 si SGK1 transfection showed a reversal of the si SGK1-induced cellular apoptosis. CONCLUSION: Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation. AIM: 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 The interaction between SGK1 and the signaling molecule was assessed by coimmunoprecipitation .RESULTS: SGK1 expression was significantly increased in the inflamed epithelial of (IEC, U0126) in intestinal epithelial cells 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, silenc ing of SGK1 by small interference RNA (si SGK1) significantly inhibited the phosphorylation of mitogen-activated protein kinase kinase 1 (MEK1) and the downstream molecule of 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 (ie, U0126) before si SGK1 transfection showed a reversal of the si SGK1 -induced cellular apoptosis. CONCLUSION: Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partially by triggering MEK / ERK activation.