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Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.
- Source :
-
Journal of cellular physiology [J Cell Physiol] 2018 May; Vol. 233 (5), pp. 4272-4281. Date of Electronic Publication: 2017 Dec 26. - Publication Year :
- 2018
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Abstract
- 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 ∼4 dyn/cm <superscript>2</superscript> 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.<br /> (© 2017 Wiley Periodicals, Inc.)
- Subjects :
- Animals
Cell Proliferation genetics
Epithelial Cells cytology
Epithelial Cells metabolism
Gene Expression Regulation, Developmental
Hepatectomy
Hepatocytes cytology
Hepatocytes metabolism
Humans
Liver metabolism
Liver surgery
Mice
Rats
Stem Cells cytology
Stress, Mechanical
Transcriptional Activation
Cell Differentiation genetics
Genes, Immediate-Early genetics
Liver growth & development
Liver Regeneration genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4652
- Volume :
- 233
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Journal of cellular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 29052842
- Full Text :
- https://doi.org/10.1002/jcp.26246