Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type

Guguen‐Guillouzo, Christiane; Clément, Bruno; Baffet, Georges; Beaumont, Carole; Morel-Chany, E.; Glaise, Denise; Guillouzo, André

doi:10.1016/0014-4827(83)90107-6

Cited by 495 publications

(174 citation statements)

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“…Matrix deposition and remodeling have been implicated as key features of hepatocyte cocultures. 15,16 In our data, the gene expression of collagen-VIII correlated negatively with inductive ability of fibroblasts. This nonfibrillar, short-chain matrix protein is present in the arterioles and venules of normal liver 38 and may play an instructional role in differentiation of other cell types.…”

Section: Gene Expression Profiling Of Fibroblastsmentioning

confidence: 50%

“…14 Despite significant investigation, a complete picture of the molecular mediators of epithelial-nonparenchymal interaction in hepatocyte cocultures is unavailable. To date, the data suggest that both matrix deposition 15,16 and direct cell-cell contact play a role 10,17,18 in the "coculture effect," whereas soluble factors have proven to be largely ineffective. 14,19,20 Two promising candidate cell surface proteins are epithelial cadherin (E-cadherin) 17 and liverregulating protein 9 ; however, NPCs lacking E-cadherin and liver-regulating protein retain the ability to support hepatic functions, suggesting that neither is the sole mediator of the "coculture effect."…”

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Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling

et al. 2004

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Cocultivation of primary hepatocytes with a plethora of nonparenchymal cells (from within and outside the liver) has been shown to support hepatic functions in vitro. Despite significant investigation into this phenomenon, the molecular mechanism underlying epithelial-nonparenchymal interactions in hepatocyte cocultures remains poorly understood. In this study, we present a functional genomic approach utilizing gene expression profiling to isolate molecular mediators potentially involved in induction of liver-specific functions by nonparenchymal cells. Specifically, primary rat hepatocytes were cocultivated with closely related murine fibroblast cell types (3T3-J2, NIH-3T3, mouse embryonic fibroblasts) to allow their classification as "high," "medium," or "low" inducers of hepatic functions. These functional responses were correlated with fibroblast gene expression profiles obtained using Affymetrix GeneChips. Microarray data analysis provided us with 17 functionally characterized candidate genes in the cell communication category (cell surface, extracellular matrix, secreted factors) that may be involved in induction of hepatic functions. Further analysis using various databases (i.e., PubMed, GenBank) facilitated prioritization of the candidates for functional characterization. We experimentally validated the potential role of two candidates in our coculture model. The cell surface protein, neural cadherin (N-cadherin), was localized to hepatocyte-fibroblast junctions, while adsorbed decorin up-regulated hepatic functions in pure cultures as well as cocultures with low-inducing fibroblasts. In the future, identifying mediators of hepatocyte differentiation may have implications for both fundamental hepatology and cell-based therapies (e.g., bioartificial liver devices). In conclusion, the functional genomic approach presented in this study may be utilized to investigate mechanisms of cell-cell interaction in a variety of tissues and disease states.

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Section: Gene Expression Profiling Of Fibroblastsmentioning

confidence: 50%

mentioning

confidence: 99%

Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling

et al. 2004

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“…June 1991 tionai culture and in co-culture with rat liver epitheliai ceils, as described previously [24]. The culture medium consisted of 75% minimal essential medium and 23% Medium 199. containing 1 mg/mi bovine serum albumin, fO&mi bovine insulin and 10% fetal calf serum (control medium).…”

Section: Febs Lettersmentioning

confidence: 99%

Regulation of glutathione S‐transferase gene expression by phenobarbital in cultured adult rat hepatocytes

et al. 1991

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Previous studies, by using Northern blotting analyses, showed that phenobarbital (PB) affects the steady-state mRNA levels of glutathione S-transferase (GST) subunits l/2, 314 and 7 in both conventional cultures of adult rat hepatocytes and cotuttures, with rat liver epithelial cells [Vandenberghe ct al., 1989, FEW Lett. 2.51, 59-64;Morel et al., 1989, FEBS Lett. 258, 99-1021. To determine whether PB acts at the transcriptional level, nuclear 'run-on' experiments using cDNA probes hybridizing to GST subunits l/2, 3/4 and 7 mRNA were performed on purified nuclei isolated from control and PI3 treated hepatocytes seeded under conventional and co-culture conditions. Data from this study demonstrate that the increase in steady-state mRNA levels observed in both conventionai cuIture and co-culture after 4 days PB exposure results from an increased tmns~ptional activity of the GST genes. However, a substantial increase in steady-state mRNA levels in the absence of a commensurate increase in transcriptional activity at 12 days of co-culture, indicates that the barbiturate has also a skbilizing effect in vitro on the GST mRNAs.Glutathione S-transferase; Gene transcription; Rat hepatocyte; Primary culture; Phenobarbital 1, INTRODUCTIONPhenobarbital (PB) has previously been reported to alter the expression, regulation and activity of several liver drug metabolizing enzymes [l-3]. Most attention has been paid to its effect on cytochrome P-450 [4-61, UDP-glucuronyltransferase [7,8] and glutathione Stransferase enzymes [9-l 11, However, it is yet not clear how this compound affects the regulation of expression of these enzymes. It is not known whether PB induction of transcriptional and translational activities involves one or more receptors [12,13].It has been shown that PB does not elevate alf cytochrome P-450 enzymes to the same extent. Cytochrome P-450 IIBI and III32 are the major liver enzymes to be induced [ 14,151. The rapid increase in the rates of transcription and the appearance of elevated Ievels of nuclear pre-mRNA and cytoplasmi~ mRNAs unequivocaily demonstrated that PB elevates levels of cytochrome P-450 III& and IIBz primarily by augmenting th: rate of transcription of the respective genes Rat bcpatocytes were isolated from Sprague-Dawley rats (ISO-ZOO 11, 1348 Mont-St-Guibert, Belgium. Fax: (32) (10) 450290. g) as described by Gugucn et al. [23). I'hcy were sccdcd in convcnm result from an increased transcriptional activity as found for the intact liver. Liver glutathione ~-transferase subunits 1 and 3 especially are also induced by PB treatment Ill]. Recently, Pickett et al. [20] reported that the increase of GST mRNA in total liver after PB addition results from an elevated GST gene transcription. In cultured hepatocytes, PB treatment induces the GST enzymatic activity 121,223. It was shown in previous study [21] that, by supplementing the culture medium with 3.2 mM PB, concentrations of individual GST subunits and GST steady-state mRNA levels were changed. However, no information is available on the re...

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“…However, liver parenchymal cells are able to synthesize their own collagen biomatrix in culture [56]. Albumin synthesis can be sustained in long term cultures (~20 days) by co-culturing liver parenchymal cells with another liver epithelial cell type [57,58], however in these studies it is clear that the rate of albumin synthesis increases during maintenance in culture to peak values at 10 days in the presence of fetal calf serum which may reflect hormonal induction, and also a partial recovery of rates of synthesis and secretion to those found in vivo.…”

Section: Loss Of Phenotype Of Cells In Suspension or Short Term Culturementioning

confidence: 99%

Primary culture, cellular stress and differentiated function

Wolffe

Tata

1984

FEBS Letters

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Isolation of specialized cell types for the analysis of tissue‐specific gene function often results in loss of the differentiated phenotype. Examples of this type of phenotypic change following tissue disaggregation are reviewed together with possible explanations. Close similarities between the effects of cell isolation with those of other cellular stresses such as heat or anoxia point to common biochemical mechanisms being involved. This suggests that the study of freshly isolated cells will contribute significantly to out understanding of the nature of cellular stress and its consequences for the maintenance of phenotype and induction of tissue specific gene expression.

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Maintenance and reversibility of active albumin secretion by adult rat hepatocytes co-cultured with another liver epithelial cell type

Cited by 495 publications

References 14 publications

Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling

Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling

Regulation of glutathione S‐transferase gene expression by phenobarbital in cultured adult rat hepatocytes

Primary culture, cellular stress and differentiated function

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