In vivo response of perisinsoidal (ITO) cells to cholestatic liver injury

Hines, Julie E.; Johnson, Sarah J.; Burt, Alastair D.

doi:10.1016/0168-8278(91)91130-9

Cited by 58 publications

(120 citation statements)

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“…Surprisingly, even after bile duct ligation, f3-PDGFR mRNA expression returned to near normal within 1 wk, even though cholestasis persists. This finding reinforces the possibility that receptor induction in the bile duct obstruction model does not result from cholestasis per se, but rather from transient mononuclear cell infiltration, which peaks 3 d after duct ligation (40).…”

Section: Discussionsupporting

confidence: 75%

“…Carbon tetrachloride results in extensive parenchymal injury due to membrane disruption, with a marked inflammatory response (1,39). In contrast, parenchymal injury and inflammation are present but more subtle in rats with bile duct obstruction (40). On the other hand, the return to normal of g-PDGFR mRNA expression within 1 wk after a single dose of CCL is consistent with the known reversibility of this lesion in the absence of repeated dosing.…”

Section: Discussionsupporting

confidence: 65%

See 1 more Smart Citation

Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.

Wong¹,

Yamasaki²,

Johnson³

et al. 1994

J. Clin. Invest.

284

197

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Section: Discussionsupporting

confidence: 75%

Section: Discussionsupporting

confidence: 65%

Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.

Wong¹,

Yamasaki²,

Johnson³

et al. 1994

J. Clin. Invest.

284

197

View full text Add to dashboard Cite

show abstract

“…51,52 In spite of the increased number of target cells after induction of fibrosis, the liver accumulation of M6P 21 -BSA was not significantly increased in fibrotic rats as compared with normal rats. A reason for this may be that in a diseased liver, a competition may occur between M6P- HEPATOLOGY Vol.…”

Section: Discussionmentioning

confidence: 99%

Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells

et al. 1999

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The hallmark of liver fibrosis is an increased extracellular matrix deposition, caused by an activation of hepatic stellate cells (HSC). Therefore, this cell type is an important target for pharmacotherapeutic intervention. Antifibrotic drugs are not efficiently taken up by HSC or may produce unwanted side-effects outside the liver. Cell-specific delivery can provide a solution to these problems, but a specific drug carrier for HSC has not been described until now. The mannose 6-phosphate/insulin-like growth factor II (M6P/ IGF-II) receptor, which is expressed in particular upon HSC during fibrosis, may serve as a target-receptor for a potential carrier. The aim of the present study was to examine if human serum albumin (HSA) modified with mannose 6-phosphate (M6P) is taken up by HSC in fibrotic livers. A series of M6P x -modified albumins were synthetized: x ‫؍‬ 2, 4, 10, and 28. Organ distribution studies were performed to determine total liver uptake. The hepatic uptake of M6P x -HSA increased with increasing M6P density. M6P x -HSA with a low degree of sugar loading (x ‫؍‬ 2-10) remained in the plasma and accumulated for 9% ؎ 0.5% or less in fibrotic rat livers. An increase in the molar ratio of M6P: HSA to 28:1 caused an increased liver accumulation to 59% ؎ 9% of the administered dose. Furthermore, we determined quantitatively the in vivo intrahepatic distribution of M6P x -HSA using double-immunostaining techniques. An increased substitution of M6P was associated with an increased accumulation in HSC; 70% ؎ 11% of the intrahepatic staining for M6P 28

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“…Although the significance of hepatocellular necrosis in the liver fibrogenesis has been proposed by Popper [29], the PS-induced liver fibrosis model has been characterized by absence of an obvious hepatocellular necrosis [27]. In general, several findings such as presence of α-SMA -positive cells [11], desmin-positive cells [25], and macrophages [14,16], and proliferation of elastic fibers [33] in the liver have been considered to be the results of hepatocellular necrosis. These findings were also observed in the present study, suggesting that hepatocellular necrosis/ apoptosis developed in PS-treated rat liver and those changes were undetectable by light microscopy in the 8-week-treated rats because of a small number of injured cells and rapid phagocytosis by macrophages.…”

Section: Discussionmentioning

confidence: 99%

Morphological and Immunohistochemical Studies on Porcine Serum-Induced Rat Liver Fibrosis

Shiga

Shirota

Ikeda

et al. 1997

The Journal of Veterinary Medical Science

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ABSTRACT. In order to clarify the pathogenesis of porcine serum (PS)-induced rat liver fibrosis, three experiments differing in dose of PS or duration of treatment were performed on male Fischer 344 rats. The rats were given an intraperitoneal injection of PS twice a week for 3 to 16 weeks and euthanized 7 days after the last injection for each treatment group. Liver tissues from these animals were subjected to detailed morphological and immunohistochemical examinations. Biochemical tests on treated rat serum revealed an increase in globulin concentration but no elevation in AST, ALT and ALP activities. There were no relationships among the dose of PS, the extent of fibrosis, and the anti-PS antibody titer. A number of α-smooth muscle actin-positive non-myofibroblastic cells, desmin-positive cells, and lipofuscin-laden Kupffer cells were found around the central veins and in the fibrous septa. In advanced stages of fibrosis, a proliferation of elastic fibers were observed in the septa. These findings were considered to indicate gradually occurred hepatocellular necrosis. The vascular endothelial cells in the fibrous septa expressed factor VIII-related antigen, exhibited fenestration accompanied by basement membrane formation, and were surrounded by Ito cells. Most of the portal vein branches showed hypertrophic thickening of the smooth muscle layer, resulting in narrowing of the lumen. These vascular changes suggested that hemodynamic alterations of the intrahepatic circulation induced hepatocellular necrosis/apoptosis and played an important role in the pathogenesis of porcine serum-induced liver fibrosis in rats. MATERIALS AND METHODS Animals:Fifty, 7-week-old male rats (Fischer 344/NSlc, Japan SLC Inc., Shizuoka), weighing approximately 150 g, were given an intraperitoneal injection of PS (JRH Biosciences, Lunexa, KS, U.S.A., Lot No. 4C2028) twice a week. The same lot of PS was used throughout the study. The rats were housed (two or three per cage) in polycarbonate cages and maintained under controlled conditions (temperature, 23 ± 2°C; humidity, 60 ± 5%). A commercial diet (CE-7, CLEA Japan Inc., Tokyo) and tap water were supplied ad libitum. The rats were euthanized under ether anesthesia by exsanguination via the abdominal aorta 7 days after the last injection for each treatment group. The spleen weight was measured to investigate the presence of portal hypertension and the degree of reaction against PS injection, and the mean values for control and treated groups were subjected to statistical analysis with Student's t-test. Serum samples, obtained from rats at necropsy, were stored at 20°C until analyses for biochemistry and antibody titer against PS.Experiment I: This experiment was designed to investigate time-related morphological changes of fibrosis. Rats were injected with a 0.5 ml of PS twice weekly for 3, 4, 5, 6 or 7 weeks. Control rats received 0.5 ml of physiological saline. Two treated rats and two control rats were euthanized at the time points mentioned above.

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In vivo response of perisinsoidal (ITO) cells to cholestatic liver injury

Cited by 58 publications

References 0 publications

Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.

Induction of beta-platelet-derived growth factor receptor in rat hepatic lipocytes during cellular activation in vivo and in culture.

Albumin modified with mannose 6-phosphate: A potential carrier for selective delivery of antifibrotic drugs to rat and human hepatic stellate cells

Morphological and Immunohistochemical Studies on Porcine Serum-Induced Rat Liver Fibrosis

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