Hepatocyte death following transforming growth factor-β1 addition

Oberhammer, Franziska; Fröschl, Gertraud; Tiefenbacher, Roman; Inayat-Hussain, Salmaan H.; Cain, Kelvin; Stopper, Helga

doi:10.1002/(sici)1097-0029(19960615)34:3<247::aid-jemt7>3.0.co;2-m

Cited by 17 publications

(5 citation statements)

References 48 publications

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“…Repeated administration of TGF-b did not prevent liver regeneration, but did appear to delay the onset and completion of proliferation (Russell et al, 1988). Alterations in the expression of TGF-b, in mechanisms that activate TGF-b, in TGF-b receptor expression, and in proteins that affect TGF-b-mediated transcription have all been observed during liver regeneration, suggesting a complex regulation of TGFb-mediated effects on hepatocytes and nonhepatocytes after partial hepatectomy (Braun et al, 1988;Oberhammer et al, 1996;Michalopoulos and DeFrances, 1997;Grasl-Kraupp et al, 1998;Akita et al, 2002). Given the complexity of TGF-b signaling in the liver, we have generated a hepatocyte-specific Tgfbr2 null mouse model to determine the physiologically relevant role of TGFBR2 and TGF-b signaling in hepatocytes in the regulation of liver proliferation.…”

Section: Introductionmentioning

confidence: 66%

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

et al. 2005

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The transforming growth factor b (TGF-b) signaling pathway, which is activated by the TGF-b receptor complex consisting of type I and type II TGF-b receptors (TGFBR1 and TGFBR2), regulates cell growth and death. TGF-b and components of its signaling pathway, particularly TGFBR2, have been implicated as tumor suppressor genes and important antimitogenic factors in the gastrointestinal tract and liver. An in vivo approach to study these effects has been hindered by the embryonic lethality of Tgfbr2 À/À mice and poor viability of the Tgfb1 À/À mice. Consequently, we have developed a hepatocyte-specific Tgfbr2 knockout mouse, the Alb-cre Tgfbr2 flx/flx mouse, to study the physiologically relevant effects of TGF-b signaling on epithelial cell proliferation in vivo. After 70% hepatectomy, we observed increased proliferation and an increased liver mass : body weight ratio in the Alb-cre Tgfbr2 flx/flx mice compared to Tgfbr2 flx/flx mice. We also observed decreased expression and increased phosphorylation of p130 in the livers from the Alb-cre Tgfbr2 flx/flx mice as well as increased expression of cyclin E, which is transcriptionally regulated, in part, by p130:E2F4. Consistent with these results, in a hepatocyte cell line derived from the Tgfbr2 flx/flx mice, we found that TGF-b increases the nuclear localization of E2F4, and presumably the transcriptional repression of the p130:E2F4 complex. Thus, we have demonstrated that TGF-b signaling in vivo regulates the mitogenic response in the regenerating liver, affecting the liver mass : body weight ratio after partial hepatectomy, and that these mitogenic responses are accompanied by alterations in p130 expression and phosphorylation, implicating p130 as one of the proteins regulated in vivo by TGF-b during liver regeneration.

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Section: Introductionmentioning

confidence: 66%

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

et al. 2005

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“…Interestingly, pyknosis induced by slow death in avian erythrocytes show no involvement of nucleases, and thus presumably no massive DNA fragmentation (Burgoyne, 1999). Secondly, it was suggested more than a century ago that the pyknotic state of chromatin or clumping of chromatin in dying neurons was followed by diffusion or ejection of DNA from the nucleus through the nuclear membrane (Collin, 1906-1907in Clarke, 1990, which agree with the observed release into the cytoplasm of increased amounts of fragmented DNA during late apoptosis, in cultured hepatocytes (Oberhammer et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Testicular apoptosis in feral Clarias gariepinus using TUNEL and cleaved caspase-3 immunohistochemistry

McClusky

Barnhoorn

Dyk

et al. 2008

Ecotoxicology and Environmental Safety

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This paper reports on the mechanistic basis of cellular death in the testis of Clarias gariepinus using the TUNEL and caspase-3 immunohistochemistry. It was also aimed to determine the testicular zone most suitable for the quantification of testicular apoptosis. The results showed that based on its immuno-expression patterns, activated caspase-3 has a clear and defined role in the progression of germ cell apoptosis in spermatogenically active catfish testis. Caspase-3 activation, and not TUNEL-detected DNA fragmentation, is associated with condensation of chromatin into a single mass. Testes of spermatogenically active catfish consist of spermatogenic, mature and spent tubules. Spermatogenic tubules were concluded to be the most suitable zone for the quantification of testicular cell death ratios as apoptotic events occurred predominantly in the secondary spermatocytes. The findings of this study will form the basis to link apoptotic events in the testes of C. gariepinus with the effects of EDC exposure in future studies.

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“…The percentage of necrotic and apoptotic cells obtained in MG‐63 spheroids was determined by counting at high magnification (500×) at least 500 cells of each sample in randomly selected areas. In particular, in order to distinguish apoptotic and necrotic cells, the nuclear morphological and ultrastructural parameters typical of these two kinds of cell death previously described were taken into account [11–13]. Specifically, cells whose nuclei had a uniform and homogeneous distribution of uncondensed chromatin were considered normal.…”

Section: Methodsmentioning

confidence: 99%

MG‐63 human osteosarcoma cells grown in monolayer and as three‐dimensional tumor spheroids present a different metabolic profile: a ¹H NMR study

et al. 2003

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High resolution proton nuclear magnetic resonance ( 1 H NMR) spectroscopy was used to determine if the same cell line (MG-63 human osteosarcoma cells) grown in monolayer or as small (about 50^80 W Wm in diameter), three-dimensional tumor spheroids with no hypoxic center has di¡erent metabolic characteristics. Consequently, the 1 H NMR spectra were obtained from both types of cultures and then compared. The results indicate that the type of cellular spatial array determines speci¢c changes in MG-63 cells. In particular, small but signi¢cant di¡erences in lactate and alanine indicating a perturbation in energy metabolism were observed in the two cell models. In addition, although variations in CH 2 and CH 3 groups were also seen, it is not possible at this time to establish if lipid metabolism is truly di¡erent in cells and spheroids.

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Hepatocyte death following transforming growth factor-β1 addition

Cited by 17 publications

References 48 publications

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

Testicular apoptosis in feral Clarias gariepinus using TUNEL and cleaved caspase-3 immunohistochemistry

MG‐63 human osteosarcoma cells grown in monolayer and as three‐dimensional tumor spheroids present a different metabolic profile: a ¹H NMR study

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Hepatocyte death following transforming growth factor-β1 addition

Cited by 17 publications

References 48 publications

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

Inactivation of TGF-β signaling in hepatocytes results in an increased proliferative response after partial hepatectomy

Testicular apoptosis in feral Clarias gariepinus using TUNEL and cleaved caspase-3 immunohistochemistry

MG‐63 human osteosarcoma cells grown in monolayer and as three‐dimensional tumor spheroids present a different metabolic profile: a 1H NMR study

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MG‐63 human osteosarcoma cells grown in monolayer and as three‐dimensional tumor spheroids present a different metabolic profile: a ¹H NMR study