PMID- 31967937
OWN - NLM
STAT- MEDLINE
DCOM- 20210122
LR  - 20220122
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 31
IP  - 6
DP  - 2020 Mar 15
TI  - Desmocollin-2 promotes intestinal mucosal repair by controlling 
      integrin-dependent cell adhesion and migration.
PG  - 407-418
LID - 10.1091/mbc.E19-12-0692 [doi]
AB  - The intestinal mucosa is lined by a single layer of epithelial cells that forms a 
      tight barrier, separating luminal antigens and microbes from underlying tissue 
      compartments. Mucosal damage results in a compromised epithelial barrier that can 
      lead to excessive immune responses as observed in inflammatory bowel disease. 
      Efficient wound repair is critical to reestablish the mucosal barrier and 
      homeostasis. Intestinal epithelial cells (IEC) exclusively express the desmosomal 
      cadherins, Desmoglein-2 and Desmocollin-2 (Dsc2) that contribute to mucosal 
      homeostasis by strengthening intercellular adhesion between cells. Despite this 
      important property, specific contributions of desmosomal cadherins to intestinal 
      mucosal repair after injury remain poorly investigated in vivo. Here we show that 
      mice with inducible conditional knockdown (KD) of Dsc2 in IEC (Villin-Cre(ERT2); 
      Dsc2 (fl/fl)) exhibited impaired mucosal repair after biopsy-induced colonic 
      wounding and recovery from dextran sulfate sodium-induced colitis. In vitro 
      analyses using human intestinal cell lines after KD of Dsc2 revealed delayed 
      epithelial cell migration and repair after scratch-wound healing assay that was 
      associated with reduced cell-matrix traction forces, decreased levels of integrin 
      beta1 and beta4, and altered activity of the small GTPase Rap1. Taken together, these 
      results demonstrate that epithelial Dsc2 is a key contributor to intestinal 
      mucosal wound healing in vivo.
FAU - Flemming, Sven
AU  - Flemming S
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Luissint, Anny-Claude
AU  - Luissint AC
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Kusters, Dennis H M
AU  - Kusters DHM
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Raya-Sandino, Arturo
AU  - Raya-Sandino A
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Fan, Shuling
AU  - Fan S
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Zhou, Dennis W
AU  - Zhou DW
AD  - George W. Woodruff School of Mechanical Engineering, Georgia Institute of 
      Technology, Atlanta, GA 30332.
FAU - Hasegawa, Mizuho
AU  - Hasegawa M
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Garcia-Hernandez, Vicky
AU  - Garcia-Hernandez V
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Garcia, Andres J
AU  - Garcia AJ
AD  - George W. Woodruff School of Mechanical Engineering, Georgia Institute of 
      Technology, Atlanta, GA 30332.
AD  - Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute 
      of Technology, Atlanta, GA 30332.
FAU - Parkos, Charles A
AU  - Parkos CA
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
FAU - Nusrat, Asma
AU  - Nusrat A
AD  - Department of Pathology, University of Michigan, Ann Arbor, MI 48109.
LA  - eng
GR  - R01 EB024322/EB/NIBIB NIH HHS/United States
GR  - R01 DK079392/DK/NIDDK NIH HHS/United States
GR  - R29 DK055679/DK/NIDDK NIH HHS/United States
GR  - R01 DK072564/DK/NIDDK NIH HHS/United States
GR  - P30 DK034933/DK/NIDDK NIH HHS/United States
GR  - R56 DK089763/DK/NIDDK NIH HHS/United States
GR  - R01 DK055679/DK/NIDDK NIH HHS/United States
GR  - R01 DK061379/DK/NIDDK NIH HHS/United States
GR  - R01 DK089763/DK/NIDDK NIH HHS/United States
GR  - R01 DK059888/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20200122
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Desmocollins)
RN  - 0 (Integrins)
RN  - EC 3.6.5.2 (Rap1 protein, mouse)
RN  - EC 3.6.5.2 (rap1 GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Cell Adhesion
MH  - *Cell Movement
MH  - Colitis, Ulcerative/metabolism/pathology
MH  - Desmocollins/*metabolism
MH  - Enterocytes/metabolism
MH  - Epithelial Cells/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Gene Deletion
MH  - Humans
MH  - Inflammation/pathology
MH  - Integrins/*metabolism
MH  - Intestinal Mucosa/*pathology
MH  - Mice, Inbred C57BL
MH  - *Wound Healing
MH  - rap1 GTP-Binding Proteins/metabolism
PMC - PMC7185897
EDAT- 2020/01/23 06:00
MHDA- 2021/01/23 06:00
PMCR- 2020/05/30
CRDT- 2020/01/23 06:00
PHST- 2020/01/23 06:00 [pubmed]
PHST- 2021/01/23 06:00 [medline]
PHST- 2020/01/23 06:00 [entrez]
PHST- 2020/05/30 00:00 [pmc-release]
AID - E19-12-0692 [pii]
AID - 10.1091/mbc.E19-12-0692 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2020 Mar 15;31(6):407-418. doi: 10.1091/mbc.E19-12-0692. Epub 2020 
      Jan 22.