Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver

Motoyama, Hideki; Komiya, Tohru; Thủy, Lê Thị Thanh; Tamori, Akihiro; Enomoto, Masaru; Morikawa, Hiroyasu; Iwai, Shuji; Fujii, Hideki; Hagihara, Atsushi; Kawamura, Etsushi; Murakami, Yoshiki; Yoshizato, Katsutoshi; Kawada, Norifumi

doi:10.1038/labinvest.2013.135

Cited by 51 publications

(59 citation statements)

References 42 publications

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“…In formalin-fixed paraffin embedded human live tissues, positive CRBP-1 staining was observed in lobular HSCs without reacting with smooth muscle cells and cholangiocyte positivity [70]. CRBP-1 was downregulated in human livers with advanced fibrosis, presumably due to a loss of vitamin A [64].…”

Section: Crbp-1 (Cellular Retinol Binding Protein-1)mentioning

confidence: 94%

“…The most characteristic morphologic feature of HSCs in a normal liver is their storage of vitamin A in the form of cytoplasmic retinoid droplets [4]. These cytoplasmic lipid droplets are readily identifiable in live biopsies [63,64]. Loss of retinoid is a prominent feature accompanying stellate cell activation.…”

Section: Morphologic Identificationmentioning

confidence: 99%

“…Since then, desmin has been widely used as a 'gold standard' for identifying HSCs in rodent liver. However, data of desmin on HSC studies obtained in human subjects have been contradictory [38,64,66,67]. Some studies have shown that perisinusoidal liver cells in normal adult liver tissue are devoid of desmin expression [66,68], and desmin immunostain has been reported to be negative in fibrotic human livers [67,69,70].…”

Section: Desminmentioning

confidence: 99%

“…Some studies reported no a-SMA immunoreactivity detected in normal human liver [42,73]. Expression of vimentin, vinculin, procollagens I, III, collagen IV, V, laminin, and fibronectin are identified in human HSCs [23,39,64,70].…”

Section: Alpha-sma (A-sma)mentioning

confidence: 99%

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Human hepatic stellate cell isolation and characterization

et al. 2017

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The hepatic stellate cells (HSCs) localize at the space of Disse in the liver and have multiple functions. They are identified as the major contributor to hepatic fibrosis. Significant understanding of HSCs has been achieved using rodent models and isolated murine HSCs; as well as investigating human liver tissues and human HSCs. There is growing interest and need of translating rodent study findings to human HSCs and human liver diseases. However, species-related differences impose challenges on the translational research. In this review, we focus on the current information on human HSCs isolation methods, human HSCs markers, and established human HSC cell lines.

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Section: Crbp-1 (Cellular Retinol Binding Protein-1)mentioning

confidence: 94%

Section: Morphologic Identificationmentioning

confidence: 99%

Section: Desminmentioning

confidence: 99%

Section: Alpha-sma (A-sma)mentioning

confidence: 99%

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Human hepatic stellate cell isolation and characterization

et al. 2017

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“…Androglobin is an ancient chimeric gene with high levels of expression in the testes of vertebrates (Hoogewijs et al, 2011), however, its function remains unresolved ). Yet another recently discovered globin, Cygb, is expressed in a diverse range of tissues and cell types including epithelium, fibroblast cell lineages, macrophages, neurons and muscle fibers (Oleksiewicz et al, 2011;Motoyama et al, 2014). Functions of Cygb appear similarly diverse, with roles in protection from reactive oxygen species and in nitrous oxide metabolism (Pesce et al, 2002;Singh et al, 2014).…”

Section: Recently Discovered Globin Genesmentioning

confidence: 99%

Characterisation of Duplicated Haemoglobin Genes in Bivalves

Klein¹

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Haemoglobins (Hbs) are found in virtually all phyla and are some of the most investigated proteins in biomedical sciences. These proteins exhibit an extraordinary diversity of form and function in invertebrate lineages. This provides a unique opportunity to explore the origin and evolution of Hbs yet little is known about their distribution, function and evolution in invertebrate lineages. To explore further the functions and evolution of those Hbs, recent transcriptome data for the Arcid bivalve Anadara trapezia is investigated here. This species shows the presence of duplicated Hb encoding genes suggesting that gene duplication may have been more extensive than previously thought in bivalves. This study tests the hypothesis that these duplicated genes show patterns of tissue specific expression and evidence of neofunctionalisation. This is shown here for at least three Hb encoding genes present in A. trapezia with strong tissue specific expression in haemolymph compared to other tissues. Furthermore, the expression of these genes remains unaffected by prolonged air exposure suggesting that neofunctionalisation may confer an evolutionary advantage to this bivalve. As well as the unique Hbs found in the bivalve order Arcoida, Hbs are also found in three other bivalve orders: Carditoida, Solemyoida and Veneroida. These four orders that possess Hbs provide compelling evidence for the independent evolution of these proteins in multiple bivalve lineages.To expand data on the distribution of Hbs in bivalves, a transcriptome sequence for Ctenoides ales in the order Limoida was generated in this project. Interrogation of the transcriptome shows the presence of at least three globin-like encoding genes including two Hb-like encoding genes providing preliminary evidence for another independent origin of Hb in a bivalve lineage. Overall, this study provides novel insights into the function, evolution and distribution of Hbs in bivalves by investigating two distantly related species. Results of this study are consistent with current theories that Hb diversity in bivalves is a result of repeated rounds of gene duplication providing the raw material for evolution. Investigation of hypoxic resistance also reinforces that greater expression of Hbs in haemolymph confers a physiological advantage suggesting that Hb would evolve more often in some lineages during adaptation to unfavourable environment conditions, particularlyAbstract ii hypoxia and prolonged air exposure.The finding of Hb-like encoding genes in another bivalve lineage also supports the evolution of this gene family through independent evolution and gene duplication, and gives insight into the distribution of globin genes in bivalves which is still poorly understood. The investigation of Hb genes in these bivalves also contributes to further understand the role of Hbs and provides potential novel insights for resistance in hypoxic environments, disease control and resistance to pollution in aquaculture.Abstract iii

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Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation through the release of microparticles

et al. 2015

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Liver fibrosis expanding from portal tracts and vascular remodeling are determinant factors in the progression of liver diseases to cirrhosis. In the present study, we examined the potential contribution of portal myofibroblasts (PMFs) to the vascular changes leading to cirrhosis. The analyses of liver cells based on the transcriptome of rat PMFs, compared to hepatic stellate cell HSC‐derived myofibroblasts in culture, identified collagen, type XV, alpha 1 (COL15A1) as a marker of PMFs. Normal liver contained rare COL15A1‐immunoreactive cells adjacent to the bile ducts and canals of Hering in the portal area. A marked increase in COL15A1 expression occurred together with that of the endothelial marker, von Willebrand factor, in human and rat liver tissue, at advanced stages of fibrosis caused by either biliary or hepatocellular injury. In cirrhotic liver, COL15A1‐expressing PMFs adopted a perivascular distribution outlining vascular capillaries proximal to reactive ductules, within large fibrotic septa. The effect of PMFs on endothelial cells (ECs) was evaluated by in vitro and in vivo angiogenesis assays. PMF‐conditioned medium increased the migration and tubulogenesis of liver ECs as well as human umbilical vein ECs and triggered angiogenesis within Matrigel plugs in mice. In coculture, PMFs developed intercellular junctions with ECs and enhanced the formation of vascular structures. PMFs released vascular endothelial growth factor (VEGF)A‐containing microparticles, which activated VEGF receptor 2 in ECs and largely mediated their proangiogenic effect. Cholangiocytes potentiated the angiogenic properties of PMFs by increasing VEGFA expression and microparticle shedding in these cells. Conclusion: PMFs are key cells in hepatic vascular remodeling. They signal to ECs through VEGFA‐laden microparticles and act as mural cells for newly formed vessels, driving scar progression from portal tracts into the parenchyma. (Hepatology 2015;61:1041–1055)

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Cytoglobin is expressed in hepatic stellate cells, but not in myofibroblasts, in normal and fibrotic human liver

Cited by 51 publications

References 42 publications

Human hepatic stellate cell isolation and characterization

Human hepatic stellate cell isolation and characterization

Characterisation of Duplicated Haemoglobin Genes in Bivalves

Portal myofibroblasts promote vascular remodeling underlying cirrhosis formation through the release of microparticles

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