PMID- 29052842
OWN - NLM
STAT- MEDLINE
DCOM- 20190221
LR  - 20190221
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 233
IP  - 5
DP  - 2018 May
TI  - Shear stress upregulates regeneration-related immediate early genes in liver 
      progenitors in 3D ECM-like microenvironments.
PG  - 4272-4281
LID - 10.1002/jcp.26246 [doi]
AB  - The role of fluid stresses in activating the hepatic stem/progenitor cell 
      regenerative response is not well understood. This study hypothesized that 
      immediate early genes (IEGs) with known links to liver regeneration will be 
      upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses 
      on the order of those produced from elevated interstitial flow after partial 
      hepatectomy. The objectives were: (1) to develop a shear flow chamber for 
      application of fluid stress to LPCs in 3D culture; and (2) to determine the 
      effects of fluid stress on IEG expression in LPCs. Two hours of shear stress 
      exposure at  approximately 4 dyn/cm(2) was applied to LPCs embedded individually or as 3D 
      spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared 
      against static controls. Quantitative reverse transcriptase polymerase chain 
      reaction was used to evaluate the effect of experimental treatments on gene 
      expression. Twenty-nine genes were analyzed, including IEGs and other genes 
      linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other 
      regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in 
      LPCs in response to fluid mechanical stress. LPCs maintained an early to 
      intermediate stage of differentiation in spheroid culture in the absence of the 
      hydrogel, and addition of the gel initiated cholangiocyte differentiation 
      programs which were abrogated by the onset of flow. Collectively the 
      flow-upregulated genes fit the pattern of an LPC-mediated 
      proliferative/regenerative response. These results suggest that fluid stresses 
      are potentially important regulators of the LPC-mediated regeneration response in 
      liver.
CI  - (c) 2017 Wiley Periodicals, Inc.
FAU - Nishii, Kenichiro
AU  - Nishii K
AD  - Department of Chemical, Paper and Biomedical Engineering, Miami University, 
      Oxford, Ohio.
FAU - Brodin, Erik
AU  - Brodin E
AD  - Department of Chemical, Paper and Biomedical Engineering, Miami University, 
      Oxford, Ohio.
FAU - Renshaw, Taylor
AU  - Renshaw T
AD  - Department of Chemical, Paper and Biomedical Engineering, Miami University, 
      Oxford, Ohio.
FAU - Weesner, Rachael
AU  - Weesner R
AD  - Department of Chemical, Paper and Biomedical Engineering, Miami University, 
      Oxford, Ohio.
FAU - Moran, Emma
AU  - Moran E
AD  - Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina.
FAU - Soker, Shay
AU  - Soker S
AUID- ORCID: 0000-0002-8458-9232
AD  - Wake Forest Institute for Regenerative Medicine, Winston Salem, North Carolina.
FAU - Sparks, Jessica L
AU  - Sparks JL
AUID- ORCID: 0000-0002-7800-6029
AD  - Department of Chemical, Paper and Biomedical Engineering, Miami University, 
      Oxford, Ohio.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171226
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
SB  - IM
MH  - Animals
MH  - Cell Differentiation/*genetics
MH  - Cell Proliferation/genetics
MH  - Epithelial Cells/cytology/metabolism
MH  - Gene Expression Regulation, Developmental
MH  - Genes, Immediate-Early/*genetics
MH  - Hepatectomy
MH  - Hepatocytes/cytology/metabolism
MH  - Humans
MH  - Liver/*growth & development/metabolism/surgery
MH  - Liver Regeneration/*genetics
MH  - Mice
MH  - Rats
MH  - Stem Cells/cytology
MH  - Stress, Mechanical
MH  - Transcriptional Activation
OTO - NOTNLM
OT  - BMOL
OT  - liver progenitor
OT  - mechanosensitivity
OT  - partial hepatectomy
EDAT- 2017/10/21 06:00
MHDA- 2019/02/23 06:00
CRDT- 2017/10/21 06:00
PHST- 2017/03/27 00:00 [received]
PHST- 2017/10/13 00:00 [accepted]
PHST- 2017/10/21 06:00 [pubmed]
PHST- 2019/02/23 06:00 [medline]
PHST- 2017/10/21 06:00 [entrez]
AID - 10.1002/jcp.26246 [doi]
PST - ppublish
SO  - J Cell Physiol. 2018 May;233(5):4272-4281. doi: 10.1002/jcp.26246. Epub 2017 Dec 
      26.