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Sinusoidal endothelial cell crosstalk with other liver cells
Author(s) -
DeLeve Laurie D.,
Wang Xiangdong
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.66.2
Subject(s) - paracrine signalling , hepatic stellate cell , cirrhosis , autocrine signalling , fibrosis , biology , crosstalk , microbiology and biotechnology , steatohepatitis , basement membrane , cancer research , liver disease , pathology , endocrinology , medicine , fatty liver , cell culture , receptor , disease , genetics , biochemistry , physics , optics
Hepatic sinusoidal endothelial cells (SEC) line the microcirculation and have a unique phenotype: open fenestrae clustered in sieve plates and lack of a basement membrane. In normal liver, the SEC phenotype is maintained by paracrine secretion of VEGF by hepatocytes and hepatic stellate cells (HSC) and, downstream, VEGF‐stimulated autocrine production of nitric oxide (NO) by the SEC. VEGF‐stimulated NO production by SEC also promotes HSC quiescence. Capillarization, loss of SEC fenestration and formation of a basement membrane, precedes liver fibrosis and seems to be permissive for the final common step in fibrosis: activation of HSC. If loss of the differentiated SEC phenotype precedes and permits fibrosis, characterizing dysregulation of cell‐cell crosstalk in liver disease becomes important in understanding liver fibrosis. Progressive loss of paracrine secretion of VEGF, loss of SEC VEGF receptors, and decline in SEC NO production occurs in parallel with increasing severity of liver disease in experimental models of steatosis, steatohepatitis and cirrhosis. Further elucidation of the interplay between hepatocytes, HSC and SEC may provide therapeutic strategies to prevent fibrosis.