Immunohistochemical analysis of development of desmin‐positive hepatic stellate cells in mouse liver

Nitou, Miho; Ishikawa, Katsutoshi; Shiojiri, Nobuyoshi

doi:10.1046/j.1469-7580.2000.19740635.x

Cited by 42 publications

(39 citation statements)

References 41 publications

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“…Desmin has been shown to be a marker for stellate cell differentiation. 39 This result is further confirmed by colocalization of Foxf1 expression with GFAP staining in adult liver. Although stellate cells have been suggested to arise from either the septum transversum mesoderm 15 or the neural crest cells, 16,17 our studies suggest that a subset of stellate cells are derived from the septum transversum mesenchyme.…”

Section: Discussionsupporting

confidence: 70%

Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

et al. 2003

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Previous studies have shown that haploinsufficiency of the splanchnic and septum transversum mesoderm Forkhead Box (Fox) f1 transcriptional factor caused defects in lung and gallbladder development and that Foxf1 heterozygous (؉/؊) mice exhibited defective lung repair in response to injury. In this study, we show that Foxf1 is expressed in hepatic stellate cells in developing and adult liver, suggesting that a subset of stellate cells originates from septum transversum mesenchyme during mouse embryonic development. Because liver regeneration requires a transient differentiation of stellate cells into myofibroblasts, which secrete type I collagen into the extracellular matrix, we examined Foxf1 ؉/؊ liver repair following carbon tetrachloride injury, a known model for stellate cell activation. We found that regenerating Foxf1 ؉/؊ liver exhibited defective stellate cell activation following CCl 4 liver injury, which was associated with diminished induction of type I collagen, ␣-smooth muscle actin, and Notch-2 protein and resulted in severe hepatic apoptosis despite normal cellular proliferation rates. Furthermore, regenerating Foxf1 ؉/؊ livers exhibited decreased levels of interferon-inducible protein 10 (IP-10), delayed induction of monocyte chemoattractant protein 1 (MCP-1) levels, and aberrantly elevated expression of transforming growth factor ␤1. T he Forkhead Box (Fox) family of transcription factors shares homology in the winged helix DNA binding domain, 1 and its members play important roles in cellular proliferation, differentiation, and metabolic homeostasis. [2][3][4][5][6] Haploinsufficiency of the Foxf1 gene (previously known as HFH-8 or Freac-1) in heterozygous (ϩ/Ϫ) mice causes perinatal lethality from pulmonary hemorrhage and severe defects in alveolarization, vascularization, and fusion of lung lobes. 7-9 Lung hemorrhage was observed in one half of newborn Foxf1 ϩ/Ϫ mice that had an 80% reduction in pulmonary Foxf1 levels (low Foxf1 ϩ/Ϫ) and reduced expression of genes involved in lung morphogenesis. 7 Interestingly, expression of these lung developmental genes was unchanged in 40% of the newborn Foxf1 ϩ/Ϫ mice that had near wildtype (WT) pulmonary levels of Foxf1 messenger RNA (mRNA) (high Foxf1 ϩ/Ϫ mice) without pulmonary hemorrhage, but they exhibited diminished alveolar septation. 7 Moreover, the high Foxf1 ϩ/Ϫ mice had normal life spans and adult lung morphology, suggesting that these mice compensated for the alveolar septation defect but exhibited defective lung repair in response to injury. 10 Liver development initiates at 9 days postcoitum (dpc) of mouse embryogenesis, when the cardiac mesenchyme induces the hepatic primordium to emerge from the foregut endoderm that invades the septum transversum mesenchyme. 6 Previous expression studies have shown

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Section: Discussionsupporting

confidence: 70%

Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

et al. 2003

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“…As shown previously, E-cadherin is specifically expressed in hepatoblasts (22,23). Nitou et al (23) isolated E-cadherinϩ cells from E12.5 mouse liver by using Dynabeads and enriched E-cadherinϩ cells to 98% purity.…”

Section: Discussionmentioning

confidence: 99%

“…Dlkϩ cells from E14.5 mouse fetal liver were able to differentiate into both hepatocytes and biliary epithelial cells in vitro (42). Recently, E-cadherin has been shown to be a specific cell surface marker for hepatoblasts (22,41). Nitou et al (23) indicated that E-cadherinϩ cells isolated from E12.5 mouse liver require coculture with cells of the E-cadherin-negative fraction, which includes endothelial and mesenchymal cells, for their survival and differentiation in vitro (23).…”

Section: Cd49fmentioning

confidence: 99%

New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts

Miki¹,

Tatsumi²,

Matsumoto³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatoblasts have the potential to differentiate into both hepatocytes and biliary epithelial cells through a differentiation program that has not been fully elucidated. With the aim to better define the mechanism of differentiation of hepatoblasts, we isolated hepatoblasts and established new culture systems. We isolated hepatoblasts from E12.5 fetal mouse liver by using E-cadherin. The E-cadherin+ cells expressed α-fetoprotein (AFP) and albumin (Alb) but not cytokeratin 19 (CK19). Transplantation of the E-cadherin+ cells into mice that had been subjected to liver injury or biliary epithelial injury led to differentiation of the cells into hepatocytes or biliary epithelial cells, respectively. In a low-cell-density culture system in the absence of additional growth factors, E-cadherin+ cells formed colonies of various sizes, largely comprising Alb-positive cells. Supplementation of the culture medium with hepatocyte growth factor and epidermal growth factor promoted proliferation of the cells. Thus the low-cell-density culture system should be useful to identify inductive factors that regulate the proliferation and differentiation of hepatoblasts. In a high-cell-density system in the presence of oncostatin M+dexamethasone, E14.5, but not E12.5, E-cadherin+ cells differentiated into mature hepatocytes, suggesting that unidentified factors are involved in hepatic maturation. Culture of E-cadherin+ cells derived from E12.5 or E14.5 liver under high-cell-density conditions should allow elucidation of the mechanism of hepatic differentiation in greater detail. These new culture systems should be of use to identify growth factors that induce hepatoblasts to proliferate or differentiate into hepatocytes and biliary epithelial cells.

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“…Desmin could be regarded as a marker of HSC [14] , and α-SMA as the marker of activation of HSC [15] . α-SMA is a kind of filament protein which is about 7 nm in diameter and mainly exists in smooth muscle cells as a portion of cytoplasm framework and a functional unit of cell contraction.…”

Section: A B a Bmentioning

confidence: 99%

Influence of serum collected from rat perfused with compoundBiejiaruangandrug on hepatic stellate cells

Shun-gen¹

2004

WJG

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AIM:To observe the effect of compound Biejiaruangan decoction (CBJRGC) (composite prescription of Carapax trionycis for softening the liver) on proliferation, activation, excretion of collagen and cytokine of hepatic stellate cells (HSCs) and to find the mechanism of prevention and treatment of hepatic fibrosis by CBJRGC. METHODS:Using MTT, immunohistochemistry and image analysis technology, the related indexes for proliferation, activation, excretion of collagen and cytokine of hepatic stellate cells were detected in 24 h, 48 h, and 72 h after adminstration of different dosages of CBJRGC. RESULTS:Statistical analysis showed that serum collected from rat perfused with CBJRGC could restrain the proliferation of HSC in 48 h and 72 h especially in high and medium dosage groups, markedly decrease the expression of desmin, synapsin and platelet derived growth factor (PDGF) in HSC in 24 h, 48 h and 72 h, as well as the expression of α-SMA, collagen III, TIMP and TGFβ1 in 48 h and 72 h, decrease the excretion of collagen I in 72 h. CBJRGC serum had no significant effect on collagens I, III and TIMP in 24 h. CONCLUSION:CBJRGC serum has a good curative effect on hepatic fibrosis. Its main mechanism may be related to the following factors. The drug serum can restrain the proliferation and activation of HSC, decrease the number of activated HSC and the total number of HSC, the excretion of collagens I, III, enhance the degradation of collagen and restore the balance of synthesis and degradation of collagen, inhibit the expression of transforming growth factor β1 (TGFβ1) and platelet derived growth factor (PDGF) in HSC, block and delay the process of hepatic fibrosis. Synapsin is a new marker of activation of HSC, which provides a theoretical and testing basis for neural regulation in the developing process of hepatic fibrosis.Guo SG, Zhang W, Jiang T, Dai M, Zhang LF, Meng YC, Zhao LY, Niu JZ. Influence of serum collected from rat perfused with compound Biejiaruangan drug on hepatic stellate cells.

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Immunohistochemical analysis of development of desmin‐positive hepatic stellate cells in mouse liver

Cited by 42 publications

References 41 publications

Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

Foxf1 +/− mice exhibit defective stellate cell activation and abnormal liver regeneration following CCl4 injury

New primary culture systems to study the differentiation and proliferation of mouse fetal hepatoblasts

Influence of serum collected from rat perfused with compoundBiejiaruangandrug on hepatic stellate cells

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