Mechanical Stretch Increases Expression of CXCL1 in Liver Sinusoidal Endothelial Cells to Recruit Neutrophils, Generate Sinusoidal Microthombi, and Promote Portal Hypertension.

ABSTRACT:

Background & aims

Mechanical forces contribute to portal hypertension (PHTN) and fibrogenesis. We investigated the mechanisms by which forces are transduced by liver sinusoidal endothelial cells (LSECs) into pressure and matrix changes.

Methods

We isolated primary LSECs from mice and induced mechanical stretch with a Flexcell device, to recapitulate the pulsatile forces induced by congestion, and performed microarray and RNA-sequencing analyses to identify gene expression patterns associated with stretch. We also performed studies with C57BL/6 mice (controls), mice with deletion of neutrophil elastase (NE^-/-) or peptidyl arginine deiminase type IV (Pad4^-/-) (enzymes that formation of neutrophil extracellular traps [NETs]), and mice with LSEC-specific de

SUBMITTER: Hilscher MB 

PROVIDER: S-EPMC6581607 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature