Common antigens of mouse oval and biliary epithelial cells. Expression on newly formed hepatocytes

Engelhardt, N; Factor, Valentina M.; Yasova, Alla K.; Полторанина, В. С.; Баранов, В. Н.; Lasareva, Maria N.

doi:10.1111/j.1432-0436.1990.tb00453.x

Cited by 83 publications

(61 citation statements)

References 21 publications

(19 reference statements)

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“…23 Among the known rat oval cell markers, A6 was the most similar to BDS7. 18 Engelhardt et al 24 reported that the A6 antigen was found only on the oval and ductal cells. In normal adult liver, A6 immunohistochemistry is reported to stain only ductal epithelial cells with no other cell type showing reactivity to the epitope.…”

Section: Discussionmentioning

confidence: 99%

Mouse A6–positive hepatic oval cells also express several hematopoietic stem cell markers

et al. 2003

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Hepatic oval cells (HOC) are thought to be a type of facultative stem cell that arises as a result of certain forms of hepatic injury. A new and more efficient model has been established to activate the oval cell compartment in mice by incorporating 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) in a standard chow at a concentration of 0.1%. At the present time, very few markers exist for the mouse oval cells. One accepted marker is A6, an uncharacterized epitope recognized by mouse hepatic oval cells and it is accepted to be an oval cell marker. Sca-1 is a cell surface marker used to identify hematopoietic stem cells in conjunction with Thy-1؉, CD34؉, and lineage-specific markers. Both the CD34 and Sca-1 antigens are not normally expressed in adult liver, but are expressed in fetal liver, presumably on the hematopoietic cells. We report herein that mouse oval cells express high levels of Sca-1 and CD34, as well as CD45 surface proteins. Immunohistochemistry revealed that the cells expressing Sca-1/CD34/CD45 were indeed oval cells because they co-expressed the oval cell-specific marker A6 (94.57% ؎ 0.033%), as well as alpha-fetoprotein (AFP) (75.92% ؎ 0.071%). By using Sca-1 antibody in conjunction with magnetic activated cell sorting (MACS), followed with a flow cytometric cell sorting (FACS) method for CD34 and CD45, we have developed a rapid oval cell isolation protocol with high yields of greater than 90%. In conclusion, we have an efficient murine model for the production and isolation of large numbers of highly purified oval cells. Our system works with most strains of mouse, which will facilitate both in vivo and in vitro studies of mouse hepatic oval cells. ( T he majority of the information on hepatic oval cells (HOCs) is derived from a series of highly reproducible rat models developed over the years. Until recently, murine models for oval cell activation and proliferation have been complicated and arduous, producing low numbers of oval cells with varying results. This has greatly limited the usefulness of mice as a genetic system to study the mechanisms of oval cell activation and differentiation. To take advantage of the immense power of mouse genetics we sought to define a reproducible, strain-independent, high-yield model for murine oval cell proliferation and purification. Recently, a method was described that is reproducible and generates large numbers of murine oval cells based on morphology. The model used to activate the oval cell compartment in mice is a diet of 3,5-diethoxycarbonyl-1,4-dihydro-collidine (DDC) at a concentration of 0.1% in a standard rodent chow for 4 to 6 weeks. Morphologically, the mouse oval cells share many similarities to rat oval cells; they are small in size (approximately 10 m), with a large nucleus to cytoplasm ratio. They radiate from the periportal region forming primitive ductular structures with poorly defined lumen, like that observed in the various rat models. [1][2][3] We used this diet, combined with antibody-based oval cell isolation techniques, to produce...

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Section: Discussionmentioning

confidence: 99%

Mouse A6–positive hepatic oval cells also express several hematopoietic stem cell markers

et al. 2003

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“…À cells, which can be regarded as a fraction of newly formed hepatocytes (Engelhardt et al 1990;Ishikawa et al 2012), were clearly detected adjacent to A6 + CK19 + LPCs in FGF7 Tg mouse livers as well as in DDC-injured livers ( Fig. 5D; Supplemental Fig.…”

Section: Ck19mentioning

confidence: 98%

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

et al. 2013

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The liver is a unique organ with a remarkably high potential to regenerate upon injuries. In severely damaged livers where hepatocyte proliferation is impaired, facultative liver progenitor cells (LPCs) proliferate and are assumed to contribute to regeneration. An expansion of LPCs is often observed in patients with various types of liver diseases. However, the underlying mechanism of LPC activation still remains largely unknown. Here we show that a member of the fibroblast growth factor (FGF) family, FGF7, is a critical regulator of LPCs. Its expression was induced concomitantly with LPC response in the liver of mouse models as well as in the serum of patients with acute liver failure. Fgf7-deficient mice exhibited markedly depressed LPC expansion and higher mortality upon toxin-induced hepatic injury. Transgenic expression of FGF7 in vivo led to the induction of cells with characteristics of LPCs and ameliorated hepatic dysfunction. We revealed that Thy1 + mesenchymal cells produced FGF7 and appeared in close proximity to LPCs, implicating a role for those cells as the functional LPC niche in the regenerating liver. These findings provide new insights into the cellular and molecular basis for LPC regulation and identify FGF7 as a potential therapeutic target for liver diseases.

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“…31 Five-micrometer frozen sections from livers embedded in Tissue-Tek Optimal Cutting Temperature Compound (Sakura Finetek USA, Torrance, CA) were fixed in methanol:acetone (1:1) for 10 minutes and then air dried for 10 minutes. Endogenous peroxidase in liver sections was quenched by emersion in 3% H 2 O 2 for 2 minutes.…”

Section: A6 Immunolocalization and Quantificationmentioning

confidence: 99%

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

Pritchard

Nagy

2010

The American Journal of Pathology

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The transcription factor early growth response (Egr)؊1 regulates the expression of genes required for execution of the wound healing response. Multiple cycles of injury, coupled to incomplete wound healing, lead to fibrosis. Therefore, we hypothesized that Egr-1 is required for the development of hepatic fibrosis. To test this hypothesis, we exposed wildtype and egr-1 ؊/؊ mice to acute or chronic carbon tetrachloride (CCl 4 ). Acute CCl 4 exposure established a profibrotic milieu in the liver, including activation of hepatic stellate cells as well as expression of type 1 collagen genes and tissue inhibitor of matrix metalloproteinase 1 in both wild-type and egr-1 ؊/؊ mice. This response was exacerbated in egr-1 ؊/؊ mice. After chronic CCl 4 exposure, hepatic fibrosis was established in both genotypes; however, the fibrotic response was profoundly worsened in Egr-1-deficient mice. Importantly, enhanced fibrosis in egr-1 ؊/؊ mice was accompanied by a robust activation of the oval cell response, suggesting more severe liver injury and/or reduced hepatocyte proliferation when compared with wild-type mice. Hepatic expression of genes indicative of oval cell activation, as well as the number of cells expressing A6, a mouse oval cell marker, was greater in egr-1 ؊/؊ mice. Taken together, these data reveal novel roles for Egr-1 as a negative regulator of both CCl 4 -induced hepatic fibrosis and the oval cell response.

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Common antigens of mouse oval and biliary epithelial cells. Expression on newly formed hepatocytes

Cited by 83 publications

References 21 publications

Mouse A6–positive hepatic oval cells also express several hematopoietic stem cell markers

Mouse A6–positive hepatic oval cells also express several hematopoietic stem cell markers

FGF7 is a functional niche signal required for stimulation of adult liver progenitor cells that support liver regeneration

Hepatic Fibrosis Is Enhanced and Accompanied by Robust Oval Cell Activation after Chronic Carbon Tetrachloride Administration to Egr-1-Deficient Mice

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