Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis

Ballardini, G.; Fallani, M; Biagini, G.; Bianchi, Francesco; Pisi, E

doi:10.1007/bf02890000

Cited by 144 publications

(72 citation statements)

References 18 publications

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“…STI571 not only caused a decrease in the number of desmin-positive cells but also in the intensity of desmin immunolabeling. In the present study, as noted before (Ballardini et al, 1988;Geerts et al, 1991), initial injury was accompanied by a marked increase in the intensity of sinusoidal desmin immunoreactivity, indicating that upregulation of desmin expression is an early feature of HSC activation. Because PDGF-BB has the ability to stimulate myofibroblastic differentiation in different cell types such as fibrocytes (Oh et al, 1998), the inhibitory effect of STI571 on desmin expression in bile duct-ligated rats may also be attributed to an inhibition of PDGF-mediated activation of HSC.…”

Section: Kinnman Et Alsupporting

confidence: 77%

Hepatic Stellate Cell Proliferation is an Early Platelet-Derived Growth Factor-Mediated Cellular Event in Rat Cholestatic Liver Injury

Kinnman

Goria

Wendum

et al. 2001

Laboratory Investigation

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SUMMARY:After liver injury, hepatic stellate cells (HSC) undergo a pleiotropic response termed "activation" that also occurs in culture models and ultimately leads to the conversion of HSC into myofibroblasts expressing smooth muscle ␣-actin (␣-SMA). The onset of HSC proliferation in primary culture coincides with the induction of platelet-derived growth factor receptor-␤ (PDGFR-␤) expression, while platelet-derived growth factor (PDGF) is the most potent mitogen for culture-activated HSC. Yet, the mechanisms and the stage of activation required for HSC proliferation in the intact liver are still uncertain. In the present study, we analyzed the proliferative response of HSC to rat cholestatic liver injury and the role of PDGF in this response. After in vivo incorporation of bromodeoxyuridine (BrdU), pure vitamin A-containing HSC were isolated at different time points after bile duct ligation (BDL) or sham operation and were analyzed by means of flow cytometry. The induction of HSC proliferation, as ascertained by BrdU incorporation, occurred between 24 and 48 hours and reached a plateau as soon as 48 hours after BDL. Flow cytometry and immunoblot analyses of HSC indicated that the induction of proliferation in HSC coincided with the up-regulation of PDGFR-␤ protein on their surface but preceded that of ␣-SMA. A dose-dependent inhibition of PDGF-BBinduced HSC proliferation by STI571, a PDGF receptor tyrosine kinase inhibitor, was documented in vitro. Daily intraperitoneal injections of STI571 (20 mg/kg) caused a 60% reduction in BrdU positive isolated HSC and in the amount of desminimmunoreactive sinusoidal cells on liver tissue sections in 48-hour bile duct-ligated rats. These results indicate that cholestatic liver injury elicits an early proliferative response in HSC that is mainly mediated by PDGF, and which precedes HSC phenotypic conversion into myofibroblasts. (Lab Invest 2001, 81:1709 -1716.

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Section: Kinnman Et Alsupporting

confidence: 77%

Hepatic Stellate Cell Proliferation is an Early Platelet-Derived Growth Factor-Mediated Cellular Event in Rat Cholestatic Liver Injury

Kinnman

Goria

Wendum

et al. 2001

Laboratory Investigation

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“…We then compared the expression pattern of nestin to that of desmin, vimentin, GFAP, and ␣SMA. In previous studies, it has been shown that expression of desmin, vimentin, and ␣SMA was [4][5][6] and that of GFAP downregulated [8][9][10] in activated stellate cells. As shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…This leveling-off is somewhat unexpected, because upregulation of desmin and vimentin has been thought to be a characteristic of activation of stellate cells. [4][5][6] ␣SMA increased continuously during the 13 days of observation. This confirms the generally held view that this actin isoform is a good marker for activation of stellate cells.…”

Section: Discussionmentioning

confidence: 98%

“…Taken Hepatic stellate cells exert specific liver functions: storage of large amounts of retinyl esters, synthesis and breakdown of hepatic extracellular matrix, secretion of a variety of cytokines, and control of the diameter of the sinusoids. 1,2 Based on the observation that stellate cells express desmin and smooth muscle ␣-actin (␣SMA), [3][4][5][6] a myogenic origin of these cells was assumed. 3 This hypothesis became doubtful when it was reported that stellate cells also express glial fibrillary acidic protein (GFAP) [7][8][9][10] and neural cell adhesion molecule (N-CAM).…”

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confidence: 99%

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Class Vi Intermediate Filament Protein Nestin Is Induced During Activation of Rat Hepatic Stellate Cells

Niki¹,

Pekny

Hellemans³

et al. 1999

Hepatology

262

169

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Hepatic stellate cells are considered to be liver-specific pericytes that play a key role in liver fibrosis. Because these cells express desmin and smooth muscle ␣-actin, they were assumed to be of myogenic origin. This hypothesis became doubtful when it was reported that stellate cells also express glial fibrillary acidic protein and neural cell adhesion molecule. In the present study, we show that activated stellate cells express nestin, a class VI intermediate filament protein originally identified as a marker for neural stem cells. Expression of nestin was first studied during spontaneous activation of stellate cells in culture. Immunohistochemistry showed that nestin-positive stellate cells already appeared at day 3, and nearly all the cells became positive for nestin at day 6 and 15. The immunoreaction was present in filaments except in dividing cells. The presence of messenger RNA transcript for nestin was shown by reverse transcription polymerase chain reaction and sequencing of amplified complementary DNA. We then compared the presence of nestin with that of other intermediate filament proteins and smooth muscle ␣-actin. Immunoblotting showed that the relative concentrations of nestin, desmin, and vimentin increased between day 2 and 6 in primary culture. After the initial increase vimentin leveled off, while nestin and desmin showed a tendency to decrease. This pattern was quite different from that of glial fibrillary acidic protein, which kept declining, and smooth muscle ␣-actin, which increased continuously up to day 13 in culture. We then studied the presence of nestin in normal and CCl 4 -injured rat liver. In normal liver, minimal immunoreaction for nestin was observed within the liver parenchyma. During induction of fibrosis by carbon tetrachloride, nestin-positive stellate cells appeared at 6 weeks, which was late in comparison with the induction of desmin and smooth muscle ␣-actin. We conclude that nestin is induced in stellate cells during transition from the quiescent to the activated phenotype; culture activation is a stronger stimulus than in vivo activation by injection of CCl 4 . Taken Hepatic stellate cells exert specific liver functions: storage of large amounts of retinyl esters, synthesis and breakdown of hepatic extracellular matrix, secretion of a variety of cytokines, and control of the diameter of the sinusoids.

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“…Early experiments demonstrated evolution of an actin-containing population of cells during focal liver and carbon tetrachloride (CCl,) injury (Ogawa et al, 1986;Ballardini et al, 1988). Further studies, employing both dimethylnitrosamine (DMN)-or CC1,-induced liver injury revealed a population of smooth muscle a actin containing cells predominantly in areas of fibrosis, but also in areas of regeneration and necrosis (Jezequel et al, 1990;Ramadori et al, 1990).…”

Section: Smooth Muscle a Actinmentioning

confidence: 99%

Cytoskeleton of liver perisinusoidal cells (lipocytes) in normal and pathological conditions

Rockey

Friedman

1992

Cell Motil. Cytoskeleton

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Desmin and actin in the identification of Ito cells and in monitoring their evolution to myofibroblasts in experimental liver fibrosis

Cited by 144 publications

References 18 publications

Hepatic Stellate Cell Proliferation is an Early Platelet-Derived Growth Factor-Mediated Cellular Event in Rat Cholestatic Liver Injury

Hepatic Stellate Cell Proliferation is an Early Platelet-Derived Growth Factor-Mediated Cellular Event in Rat Cholestatic Liver Injury

Class Vi Intermediate Filament Protein Nestin Is Induced During Activation of Rat Hepatic Stellate Cells

Cytoskeleton of liver perisinusoidal cells (lipocytes) in normal and pathological conditions

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