PMID- 38006803
OWN - NLM
STAT- MEDLINE
DCOM- 20240101
LR  - 20240106
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 690
DP  - 2024 Jan 1
TI  - Protective effects of metformin in the pro-inflammatory cytokine induced 
      intestinal organoids injury model.
PG  - 149291
LID - S0006-291X(23)01385-2 [pii]
LID - 10.1016/j.bbrc.2023.149291 [doi]
AB  - Pathogenesis of inflammatory bowel disease (IBD) accompanies disrupted intestinal 
      tight junctions. However, many approaches of therapeutics for IBD are focused 
      only on anti-inflammatory effects and most cellular experiments are based on 
      two-dimensional cell lines which have insufficient circumstances of intestine. 
      Thus, here, we used three-dimensional structure intestinal organoids to 
      investigate effects of metformin in the in vitro IBD condition. In this study, we 
      focused on both tight junctions and the levels of inflammatory cytokines. 
      Metformin enhances the intestinal barrier in injured intestine via upregulation 
      of AMP-activated protein kinase, dysfunction of which contributes to the 
      pathogenesis of intestinal diseases. We aim to investigate the effects of 
      metformin on cytokine-induced injured intestinal organoids. Tumor necrosis 
      factor-alpha (TNF-alpha) was used to induce intestinal injury in an organoid model, 
      and the effects of metformin were assessed. Cell viability and levels of 
      inflammatory cytokines were quantified in addition to tight junction markers. 
      Furthermore, 4 kDa FITC-dextran was used to assess intestinal permeability. The 
      upregulation of inflammatory cytokine levels was alleviated by metformin, which 
      also restored the intestinal epithelium permeability in TNF-alpha-treated injury 
      organoids. We confirmed that claudin-2 and claudin-7, representative tight 
      junction markers, were also protected by metformin treatment. This study confirms 
      the protective effects of metformin, which could be used as a therapeutic 
      strategy for inflammatory intestinal diseases.
CI  - Copyright (c) 2023 Elsevier Inc. All rights reserved.
FAU - Hahn, Soojung
AU  - Hahn S
AD  - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 
      Seoul 06355, South Korea; Division of Endocrinology and Metabolism, Department of 
      Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of 
      Medicine, Seoul 06355, South Korea. Electronic address: sjhahn@skku.edu.
FAU - Kim, Gyuri
AU  - Kim G
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, 
      South Korea. Electronic address: gyuri5.kim@samsung.com.
FAU - Jin, Sang-Man
AU  - Jin SM
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06355, 
      South Korea. Electronic address: sangman.jin@samsung.com.
FAU - Kim, Jae Hyeon
AU  - Kim JH
AD  - Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 
      Seoul 06355, South Korea; Division of Endocrinology and Metabolism, Department of 
      Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of 
      Medicine, Seoul 06355, South Korea. Electronic address: jaehyeon@skku.edu.
LA  - eng
PT  - Journal Article
DEP - 20231122
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Cytokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Humans
MH  - Cytokines/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - *Metformin/pharmacology
MH  - Intestines
MH  - Intestinal Mucosa/metabolism
MH  - *Inflammatory Bowel Diseases/drug therapy/metabolism
MH  - Tight Junctions/metabolism
MH  - Organoids/metabolism
MH  - Caco-2 Cells
OTO - NOTNLM
OT  - Gut barrier
OT  - Intestinal injury
OT  - Intestinal organoids
OT  - Metformin
OT  - Tight junction
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/11/26 07:44
MHDA- 2024/01/02 11:41
CRDT- 2023/11/25 18:11
PHST- 2023/11/07 00:00 [received]
PHST- 2023/11/13 00:00 [revised]
PHST- 2023/11/17 00:00 [accepted]
PHST- 2024/01/02 11:41 [medline]
PHST- 2023/11/26 07:44 [pubmed]
PHST- 2023/11/25 18:11 [entrez]
AID - S0006-291X(23)01385-2 [pii]
AID - 10.1016/j.bbrc.2023.149291 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2024 Jan 1;690:149291. doi: 
      10.1016/j.bbrc.2023.149291. Epub 2023 Nov 22.