Histological alterations in the livers of Cx43-deficient mice submitted to a cholestasis model

Teixeira, Tarso Felipe; Silva, Tereza Cristina da; Fukumasu, Heidge; Lima, Cynthia Esteves de; Dagli, M.L.; Guerra, José Luiz

doi:10.1016/j.lfs.2007.05.017

Cited by 9 publications

(7 citation statements)

References 24 publications

(32 reference statements)

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“…Hepatic Cx26 immunoreactivity also decreases following bile duct ligation [30,31], though its mRNA content rather increases [30]. In contrast, Cx43 protein is positively affected in this model [30] and it has been reported that bile duct ligated heterozygous Cx43 +/À knock-out mice display less hepatic vein angiogenesis, while other parameters, such as biliary duct hyperplasia, remain unchanged [34]. Unlike Cx26 and Cx32, no changes in Cx43 steady-state protein levels are observed in the choledochocaval fistula rat model of complete biliary retention [31].…”

Section: Gap Junctions In Cholestasismentioning

confidence: 69%

Gap junctions and non-neoplastic liver disease

Vinken

2012

Journal of Hepatology

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Because of their critical role as goalkeepers of hepatic homeostasis, gap junctions are frequent targets in liver disease. This concept has been demonstrated on many occasions in the light of hepatocarcinogenesis. Relatively little focus has been put on the fate of gap junctions in other liver pathologies, including hepatitis, liver fibrosis and cirrhosis, cholestasis and hepatic ischemia and reperfusion injury. The present paper provides an in-depth description of the multiple changes in expression, localization and function of connexins, the molecular constituents of gap junctions. The use of connexins as biomarkers and therapeutic targets in liver disease is also illustrated.

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Section: Gap Junctions In Cholestasismentioning

confidence: 69%

Gap junctions and non-neoplastic liver disease

Vinken

2012

Journal of Hepatology

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“…Also, previous studies showed that developing bile ducts expressed Cx43 and nascent hepatocytes expressed Cx32 (Zhang and Thorgeirsson 1994;Bode et al 2002). Dexamethasone/DMSO treatment has been shown to modulate the expression of connexin family members in the GAP junctions of hepatocytes and bile duct cells (Kojima et al 1995(Kojima et al , 1997Yoshizawa et al 1997), presumably affecting liver differentiation by controlling the exchange of small molecules, although Cx knockout studies did not show any acute effect on the maintenance or function of adult liver parenchymal cells (Ott et al 2006;Teixeira et al 2007). A fuller understanding of the regulators of hepatocyte/cholangiocyte differentiation, and, in particular, the mechanisms guiding the self-assembly of cholangiocytes into defined ducts, may come from the ongoing proteomic and genomic studies of our pig liver cell culture system.…”

Section: Discussionmentioning

confidence: 99%

Culture of porcine hepatocytes or bile duct epithelial cells by inductive serum-free media

Caperna

Blomberg

Garrett

et al. 2011

In Vitro Cell.Dev.Biol.-Animal

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A serum-free, feeder cell-dependent, selective culture system for the long-term culture of porcine hepatocytes or cholangiocytes was developed. Liver cells were isolated from 1-wk-old pigs or young adult pigs (25 and 63 kg live weight) and were placed in primary culture on feeder cell layers of mitotically blocked mouse fibroblasts. In serum-free medium containing 1% DMSO and 1 μM dexamethasone, confluent monolayers of hepatocytes formed and could be maintained for several wk. Light and electron microscopic analysis showed hepatocytes with in vivo-like morphology, and many hepatocytes were sandwiched between the feeder cells. When isolated liver cells were cultured in medium without dexamethasone but with 0.5% DMSO, monolayers of cholangioctyes formed that subsequently self-organized into networks of multicellular ductal structures, and whose cells had monocilia projecting into the lumen of the duct. Gamma-glutamyl transpeptidase (GGT) was expressed by the cholangiocytes at their apical membranes, i.e., at the inner surface of the ducts. Cellular GGT activity increased concomitantly with the development of ductal structures. Cytochrome P-450 was determined in microsomes following addition of metyrapone to the cultures. In vivo-like levels of P-450s were found in hepatocyte monolayers while levels of P-450 were markedly reduced in cholangiocyte monolayers. Serum protein secretion in conditioned media was analyzed by Western blot and indicated that albumin, transferrin, and haptoglobin levels were maintained in hepatocytes while albumin and haptoglobin declined over time in cholangiocytes. Quantitative RT-PCR analysis showed that serum protein mRNA levels were significantly elevated in the hepatocytes monolayers in comparison to the bile ductule-containing monolayers. Further, mRNAs specific to cholangiocyte differentiation and function were significantly elevated in bile ductule monolayers in comparison to hepatocyte monolayers. The results demonstrate an in vitro model for the study of either porcine hepatocytes or cholangiocytes with in vivo-like morphology and function.

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“…Cx43 is the major protein subunit of gap junctions in the cell membrane (Ton and Kathryn Iovine, 2012). Tumor incidence and metastasis are related to uncontrolled proliferation and the abnormal differentiation of tumor cells (Teixeira et al 2007). Studies have revealed the positive, but significantly reduced, expression of Cx43 in tumor cells (Moore et al 2008;Solan and Lampe, 2014), resulting in the disappearance of the most important contact inhibition in tumor cells, and a decline in tumor cell binding capacity.…”

Section: Discussionmentioning

confidence: 99%

Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226

Jp¹,

Wei²

2015

Genet. Mol. Res.

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ABSTRACT. In this study, the human lung squamous carcinoma cell line NCI-H226 was transfected with the recombinant plasmid pBudCE4.1_Cx43 to explore the role of the Cx43 gene in cell growth, cell cycle, and tumor migration. pBudCE4.1-Cx43 was transfected into human lung squamous carcinoma NCI-H226 cells using Lipofectamine TM2000. The mRNA and protein expressions of Cx43 in the transfected cells were detected by reverse transcriptase polymerase chain reaction and western blot analysis. The cell-cell communication was detected using the scratch dye tracer method and the cell cycle was detected by flow cytometry. The CCK-8 proliferation, scratch healing, and cell invasion assays were performed to evaluate the effect of the Cx43 gene transfection on the proliferation, migration, and invasive abilities of NCI-H226 cells. Cx43 mRNA and protein expressions and the fluorescence intensity in the scratch healing test were significantly higher in the experimental group than those in the control and blank groups (P < 0.05 and < 0.01, respectively). The CCK-8 proliferation assay and the scratch healing experiment revealed significantly inhibited NCI-H226 cell proliferation (especially 72 h after incubation) and cell migration, respectively, in the experimental group, compared to the control and 13110-13119 (2015) blank groups (P < 0.001 and <0.05, respectively). The transwell chamber test showed a statistically significant decrease in the invasive ability of NCI-H226 cells in the experimental group (P < 0.05). Therefore, Cx43 gene transfection could inhibit the migration of human lung squamous carcinoma cell line NCI-H226, thereby inhibiting tumor cell proliferation.

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Histological alterations in the livers of Cx43-deficient mice submitted to a cholestasis model

Cited by 9 publications

References 24 publications

Gap junctions and non-neoplastic liver disease

Gap junctions and non-neoplastic liver disease

Culture of porcine hepatocytes or bile duct epithelial cells by inductive serum-free media

Effects of Cx43 gene modification on the proliferation and migration of the human lung squamous carcinoma cell line NCI-H226

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