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BioMed Research International
Volume 2017 (2017), Article ID 4097205, 9 pages
https://doi.org/10.1155/2017/4097205
Review Article

SECs (Sinusoidal Endothelial Cells), Liver Microenvironment, and Fibrosis

1Department of Chemical and Biomolecular Engineering, University of Nebraska, Lincoln, NE, USA
2Department of Biochemistry, University of Nebraska, Lincoln, NE, USA
3Nebraska Center for Integrated Biomolecular Communication, University of Nebraska, Lincoln, NE, USA
4Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, USA
5Nebraska Center for the Prevention of Obesity Diseases, University of Nebraska, Lincoln, NE, USA
6Nebraska Center for Materials and Nanoscience, University of Nebraska, Lincoln, NE, USA
7Mary and Dick Holland Regenerative Medicine Program, University of Nebraska Medical Center, Omaha, NE, USA

Correspondence should be addressed to Srivatsan Kidambi; ude.lnu@2ibmadiks

Received 1 July 2016; Accepted 16 November 2016; Published 15 February 2017

Academic Editor: Yury Popov

Copyright © 2017 Vaishaali Natarajan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Liver fibrosis is a wound-healing response to chronic liver injury such as alcoholic/nonalcoholic fatty liver disease and viral hepatitis with no FDA-approved treatments. Liver fibrosis results in a continual accumulation of extracellular matrix (ECM) proteins and paves the way for replacement of parenchyma with nonfunctional scar tissue. The fibrotic condition results in drastic changes in the local mechanical, chemical, and biological microenvironment of the tissue. Liver parenchyma is supported by an efficient network of vasculature lined by liver sinusoidal endothelial cells (LSECs). These nonparenchymal cells are highly specialized resident endothelial cell type with characteristic morphological and functional features. Alterations in LSECs phenotype including lack of LSEC fenestration, capillarization, and formation of an organized basement membrane have been shown to precede fibrosis and promote hepatic stellate cell activation. Here, we review the interplay of LSECs with the dynamic changes in the fibrotic liver microenvironment such as matrix rigidity, altered ECM protein profile, and cell-cell interactions to provide insight into the pivotal changes in LSEC physiology and the extent to which it mediates the progression of liver fibrosis. Establishing the molecular aspects of LSECs in the light of fibrotic microenvironment is valuable towards development of novel therapeutic and diagnostic targets of liver fibrosis.