LAUSR.org creates dashboard-style pages of related content for over 1.5 million academic articles. Sign Up to like articles & get recommendations!

Incomplete Differentiation of Engrafted Bone Marrow Endothelial Progenitor Cells Initiates Hepatic Fibrosis in the Rat

Photo by nci from unsplash

Normal liver sinusoidal endothelial cells (LSECs) promote quiescence of hepatic stellate cells (HSCs). Prior to fibrosis, LSECs undergo capillarization, which is permissive for HSC activation, the proximate event in hepatic… Click to show full abstract

Normal liver sinusoidal endothelial cells (LSECs) promote quiescence of hepatic stellate cells (HSCs). Prior to fibrosis, LSECs undergo capillarization, which is permissive for HSC activation, the proximate event in hepatic fibrosis. The aims of this study were to elucidate the nature of and mechanisms leading to capillarization and to determine how LSECs promote HSC quiescence and why “capillarized LSECs” lose control of HSC activation. The contribution of bone marrow (BM) endothelial progenitor cells to capillarization was identified using rats transplanted with transgenic enhanced green fluorescent protein–positive BM. Shotgun proteomics and informatics were used to identify the LSEC mediator that maintains HSC quiescence. The study shows that capillarization is due to repair of injured LSECs by BM endothelial progenitors that engraft but fail to fully mature. Lack of maturation of BM‐derived LSECs is due to cell autonomous pathways that inhibit the nitric oxide pathway. We identify heparin binding epidermal growth factor–like growth factor (HB‐EGF) as the signal that maintains HSC quiescence and show that immature LSECs are unable to shed HB‐EGF from the cytosolic membrane. Conclusion: Chronic liver injury can recruit BM progenitors of LSECs that engraft and fail to fully differentiate, which creates an environment that is permissive for hepatic fibrosis; elucidation of these early events in the fibrotic process will provide targets for treatment of hepatic fibrosis.

Keywords: progenitor cells; fibrosis; marrow endothelial; endothelial progenitor; hepatic fibrosis; bone marrow

Journal Title: Hepatology
Year Published: 2019

Link to full text (if available)


Share on Social Media:                               Sign Up to like & get
recommendations!

Related content

More Information              News              Social Media              Video              Recommended



                Click one of the above tabs to view related content.