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Cited by 47Inflammatory Bowel DiseaseOcular Diseases and Behçet’s SyndromeNF-κB Signaling Pathways

SGK1 inhibits cellular apoptosis and promotes proliferation via the MEK/ERK/p53 pathway in colitis

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Bai, Jian-An·2015·World Journal of Gastroenterology
DOI 10.3748/wjg.v21.i20.6180PMC PMC4445095
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Abstract

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 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. CONCLUSION: Our data suggested that SGK1 may protect IECs in colitis from tumor necrosis factor-α-induced apoptosis partly by triggering MEK/ERK activation.

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Cited by

Sorted by citations

Authors
Bai, J.-A.
Affiliations
Jiangsu Province Hospital (CN)
Corresponding author
Bai, Jian-An
ORCID
Bai, Jian-An
Venue
World Journal of Gastroenterology
Publisher
Baishideng Publishing Group Inc.
Published
2015
Volume
21
Issue
20
Pages
6180
ISSN
1007-9327 (ISSN-L)
DOI
10.3748/wjg.v21.i20.6180
PMC
PMC4445095
OpenAlex
W1162488638
Cited by
47
References
5
Citations by year
2026: 4 · 2025: 6 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 7 · 2020: 3 · 2019: 7 · 2018: 1 · 2017: 5 · 2016: 3 · 2015: 1
FWCI
2.29
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Gastroenterology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (81470806)
  • Government of Jiangsu Province
  • Natural Science Foundation of Jiangsu Province (81470806, BK20141496)
  • Nanjing Medical University
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
  • Health Sciences › Medicine › Ophthalmology › Ocular Diseases and Behçet’s Syndrome
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
SGK1, serum- and glucocorticoid-inducible kinase 1, Crohn's disease, colitis, MEK/ERK signaling, p53, apoptosis, cell proliferation, intestinal epithelial cells, TNBS-induced colitis, TNF-α, Bax, MEK1 inhibition
MeSH terms
Serum-Glucocorticoid Regulated Kinases, Animals, Colitis, Colon, Crohn Disease, Disease Models, Animal, Dose-Response Relationship, Drug, Epithelial Cells, Female, Humans, Intestinal Mucosa, Mice, Inbred BALB C, Rabbits, Time Factors, Transfection, Trinitrobenzenesulfonic Acid, Tumor Necrosis Factor-alpha, Signal Transduction, Tumor Suppressor Protein p53, Apoptosis, Protein Serine-Threonine Kinases, Immediate-Early Proteins, RNA Interference, HCT116 Cells, Protein Kinase Inhibitors, Extracellular Signal-Regulated MAP Kinases, MAP Kinase Kinase 1, Cell Proliferation

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