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

McGuire, Richard F.; Bissell, D. Montgomery; Boyles, J K; Roll, F J

doi:10.1002/hep.1840150603

Cited by 154 publications

(96 citation statements)

References 41 publications

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“…1-3. Others have reported that ECM composition can influence fenestration diameter 18,19 and that presented a valid argument for evaluation of ECM protein deposition in this study. Because porosity increases dramatically in the first 24 hours after PHx, survey of resident ECM proteins within the space of Disse may provide evidence for matrix control of SEC porosity in vivo.…”

Section: Resultssupporting

confidence: 63%

“…Therefore, fenestrations are not passive sieves, but are most probably very dynamic structures whose size and density have been shown to be affected by physical factors such as portal pressure and shear stress 10,11 ; soluble substances such as alcohol, 12 serotonin, 13 endotoxin, 14 and nicotine 15 ; and cytoskeletal disruption agents like cytochalasin B, 16,17 as well as the composition of the ECM. 18,19 Given the fact that SEC fenestrations can modulate their diameters in response to a variety of factors and events, we sought to examine fenestration size and sinusoidal porosity index with respect to ultrastructural changes taking place within the regenerating lobule. Here, we document the changes in fenestration diameters and porosity of SEC in the periportal (zone 1) versus pericentral (zone 3) sinusoids during regeneration, from 5 minutes to 14 days following 70% PHx.…”

mentioning

confidence: 99%

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Sinusoidal Ultrastructure Evaluated During the Revascularization of Regenerating Rat Liver

et al. 2001

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Sinusoidal endothelial cell (SEC) porosities were compared between the periportal (zone 1) and pericentral (zone 3) regions of the rat liver during regeneration following partial hepatectomy (PHx). SEC porosities and fenestration diameters were measured in control livers, as well as at 5 minutes, 24, 48, 72, 96, 120 hours, and 14 days following PHx. Bimodal maximums in both porosity and fenestration diameters were observed in both zones at 5 minutes and 5 days following PHx. SEC porosities increased significantly in both zones 1 and 3 within 5 minutes following PHx, but the increase was maintained only in zone 1 at 24 hours after resection. Following the initial rise, both zones displayed a gradual decrease to less than half their porosity values at 72 hr post-PHx. After 72 hours, porosities increased to over control levels and remained elevated until 14 days after PHx. The decrease in porosity at 72 hr post-PHx is accompanied by ultrastructural changes within the sinusoid at this time. Vascular corrosion casting and transmission electron microscopy (TEM) show sinusoid compression resulting from increased hepatic plate widths due to hepatocyte proliferation in the absence of SEC proliferation. Also at this time, we observed many SEC completely enveloped by stellate cells. The zonal variations observed for porosities throughout regeneration did not correlate with changes in laminin, collagen I and IV, or fibronectin deposition within the space of Disse. Taken together, the data reveal that SEC are dynamic regulators of porosity that respond rapidly and locally to environmental zonal stimuli during liver regeneration. (HEPATOLOGY 2001;33:363-378.)Following chemical or mechanical injury, the liver has the extraordinary capacity to regenerate back to its normal mass within a short time. During regeneration, the same physiologic functions required by the organism must be performed with less metabolic "equipment," and therefore the liver must continuously adapt its metabolic output to its rapidly changing architecture. As a result of tissue loss, the concentrations of many factors, including growth factors, cytokines, and proteases, rise in the blood and liver to promote temporal and spatial proliferation and migration of the various cells to efficiently reconstitute the liver mass (reviewed by Michalopoulos 1 and Fausto 2 ). Following 70% partial hepatectomy (PHx) in the rat, hepatocyte DNA synthesis peaks abruptly at 24 hours after PHx, and essentially terminates DNA synthesis by 72 hours following resection. 3 Sinusoidal endothelial cells (SEC), the open, fenestrated, discontinuous endothelial cells that line the vessels supplying the parenchymal plates, do not initiate DNA synthesis until 48 to 72 hours after resection, peaking at 4 d post-PHx, but continue to proliferate at least until 8 days following PHx. [3][4][5] This cellular order of proliferative events results in the formation of avascular hepatic islands throughout the liver lobule. 6 Subsequent proliferation and migration of the sinusoidal endothelium i...

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Section: Resultssupporting

confidence: 63%

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confidence: 99%

Sinusoidal Ultrastructure Evaluated During the Revascularization of Regenerating Rat Liver

et al. 2001

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“…27 In the present study, we demonstrated contraction of SEF by treating isolated SECs with ET-1. The cytoskeleton is well known to consist of three major components; microfilaments, intermediate filaments, and microtubules.…”

Section: Discussionsupporting

confidence: 59%

Endothelin-1 Suppresses Plasma Membrane Ca++-ATPase, Concomitant with Contraction of Hepatic Sinusoidal Endothelial Fenestrae

Yokomori

Oda

Ogi

et al. 2003

The American Journal of Pathology

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Intracytoplasmic free calcium ions (Ca ؉؉ ) are maintained at a very low concentration in mammalian tissue by extruding Ca ؉؉ from the cytoplasm against a steep extracellular Ca ؉؉ concentration gradient, mainly through the activity of plasma membrane Ca ؉؉ pump-ATPase. The present study aimed to elucidate how endothelin-1 (ET-1) affects the morphology of sinusoidal endothelial fenestrae and ultrastructural distribution of plasma membrane ATPases and intracytoplasmic free Ca ؉؉ in isolated rat hepatic sinusoidal endothelial cells. Sinusoidal endothelial fenestrae were observed by scanning electron microscope. Ando's electron cytochemical method was used for ultrastructural localization of Ca ؉؉ -Mg ؉؉ -ATPase activity, electron immunogold postembedding method for Ca ؉؉ pump-ATPase immunoactivity, and antimonate method for intracytoplasmic free Ca Hepatic sinusoidal endothelial cells (SECs) possess fenestrae mostly arranged in sieve plate-like pores. These fenestrae lack a diaphragm and a basal lamina and therefore are an open connection between the lumen of the sinusoid and the space of Disse. 1 They are not single and independent pores but are interconnected labyrinth-like structures. 2 Actin microfilaments and calmodulin are closely associated with the endothelial plasma membrane, suggesting that in the presence of calcium ions, calmodulin and actin microfilaments may be involved in the contraction and dilatation of endothelial cell fenestrae. [2][3][4] The Ca ϩϩ pump of the plasma membrane extrudes Ca ϩϩ from the cytoplasm against a steep extracellular concentration gradient, and is essential for homeostatic maintenance of a low concentration of intracellular Ca ϩϩ . 5 By immunofluorescence and immunoelectron microscopic study, the Ca ϩϩ pump in capillary endothelial cells and visceral smooth muscle cells is found to be 18-to 25-fold more concentrated in the invaginated caveolar membrane compared with the noncaveolar portion of the plasma membrane. 6,7 Our recently study demonstrated localization of calcium pump-dependent adenosine triphosphatase (Ca ϩϩ pump-ATPase) in hepatic sinusoidal endothelial fenestrae (SEF). 8 Endothelins (ETs) are a family of three potent vasoconstrictor peptides. ET-1 was first identified in the supernatant of cultured endothelial cells. 9 Two other forms of ET have subsequently been characterized and designated ET-2 and ET-3, which differ from ET-1 by two and six amino acids, respectively. 10,11 Recently the authors have reported that ET-1 induces contractions of the SEF not only in vivo 12 but also in vitro. 13 The present study was designed to elucidate the subcellular mechanism of SEF contraction by focusing on the electron cytochemical distribution of plasma membrane Ca ϩϩ -Mg ϩϩ -ATPase, Ca ϩϩ pump-ATPase, and intracytoplasmic free calcium ions in SECs.

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“…The ensuing perisinusoidal fibrosis constitutes the lesion known as "capillarization of the sinusoids". It is associated with loss of the open fenestrae of sinusoidal endothelial cells (McGuire et al, 1992) and effacement of the microvilli on the sinusoidal surface of hepatocytes (Orrego et al, 1979), and it correlates clinically with significantly deranged liver function (Schaffnet and Popper, 1963).…”

Section: Hepatic Stellate Cell (Hsc) Activationmentioning

confidence: 99%

Chronic liver injury, TGF-β, and cancer

Bissell

2001

Exp Mol Med

156

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Cells termed myofibroblasts are prominent in the injury response of all epithelial tissues. They exhibit proliferation, migration, production of collagen and other extracellular matrix (ECM) molecules, and contraction, all for containing the injury and closing the wound. When the injury is limited in time, the final stage of the repair involves a dismantling of the cellular apparatus and restoration of normal tissue structure. With multiple cycles of repair, however, there is net accumulation of ECM, to the detriment of tissue structure and function. Repair-related ECM coalesces into fibrous bundles and, over time, undergoes changes that render it resistant to degradation. The result is a scar. In the skin, a scar may have cosmetic importance only. In the liver, however, extensive scarring is the setting for unregulated growth and neoplasia; also, fibrous bands disrupt normal blood flow, leading to portal hypertension and its complications. With regard to therapy for fibrosis, the first consideration is elimination of the injury factor. However, given that many liver diseases do not have effective therapies at present, strategies targeting fibrogenesis per se are under development. The main source of myofibroblast-like cells and ECM production in the liver is the perisinusoidal stellate cell, which responds to injury with a pleiotypic change termed activation. Activation is orchestrated by cytokines and the ECM itself. Among the cytokines involved in this process, transforming growth factor-beta (TGF-β) is particularly prominent. The early changes in ECM include de novo production of a specific "fetal" isoform of fibronectin, which arises from sinusoidal endothelial cells. It is stimulated by TGF-β and acts directly on stellate cells to promote their activation. Based on these and other advances in understanding the fundamentals of the injury response, several strategies now exist for altering fibrogenesis, ranging from agents that block TGF-β to traditional Chinese herbal extracts. Arrest of fibrogenesis, even with underlying cirrhosis, is likely to extend life or prolong the time to transplant. Whether it reduces the risk of hepatocellular carcinoma remains to be proven. Although TGF-β antagonists are effective anti-fibrogenic agents, they will require detailed safety testing because of the finding that several forms of epithelial neoplasia are associated with altered regulation of TGF-β.

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

Cited by 154 publications

References 41 publications

Sinusoidal Ultrastructure Evaluated During the Revascularization of Regenerating Rat Liver

Sinusoidal Ultrastructure Evaluated During the Revascularization of Regenerating Rat Liver

Endothelin-1 Suppresses Plasma Membrane Ca++-ATPase, Concomitant with Contraction of Hepatic Sinusoidal Endothelial Fenestrae

Chronic liver injury, TGF-β, and cancer

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