Role of Extracellular Matrix in Regulating Fenestrations of ... : Hepatology (original) (raw)

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Role of Extracellular Matrix in Regulating Fenestrations of Sinusoidal Endothelial Cells Isolated From Normal Rat Liver

McGuire, Richard F.1,2; Bissell, Montgomery D.1,2; Boyles, Janet3,4,5; Roll, Joseph F. M.D.*,1,2

1_Liver Center, San Francisco General Hospital, University of California, San Francisco, 94110_

2_Department of Medicine, University of California, San Francisco, California 94143_

3_Department of Gladstone Foundation Laboratories for Cardiovascular Research, San Francisco, California 94143_

4_Department of Pathology, University of California, San Francisco, California 94143_

5_Cardiovascular Research Institute, University of California, San Francisco, California 94143_

* Liver Center Laboratory, Building 40, Room 4102, San Francisco General Hospital, 1001 Potrero Ave., San Francisco, CA 94110.

Received: 6 August 1990; Accepted: 16 January 1992

Abstract

Open fenestrations are a conspicuous feature of sinusoidal endothelial cells and allow free movement of plasma into the space of Disse. In hepatic fibrosis, the number of fenestrations decreases as interstitial collagen increases in the liver, a change that correlates with deposition of extracellular matrix in the space of Disse. In this study, the possibility of a causal relationship between altered fenestral morphology and perisinusoidal matrix has been examined by culturing rat sinusoidal endothelial cells on individual matrix proteins or on a native matrix consisting of human amniotic membrane with interstitial collagen (types I and III) on one side and basement membrane proteins (collagen types IV and V and laminin) on the other. Under culture conditions, individual components of the extracellular matrix failed to maintain fenestrations. A basement–membranelike gel matrix derived from the Engelbreth–Holm–Swarm tumor was similarly ineffective. Fenestral density and porosity (percentage of cell surface occupied by fenestrations) were significantly enhanced, however, when endothelial cells were cultured on the basement–membrane side of human amnion. These data suggest that support of endothelial fenestrations requires a complex matrix. In particular, physiologically derived basement membrane maintains fenestrations, whereas interstitial collagen matrix does not. The loss of fenestrations associated with hepatic fibrosis may be related in part to an accumulation of interstitial collagens in the space of Disse. (Hepatology 1992;15:989–997).