Human hepatocyte polyploidization kinetics in the course of life cycle

Kudryavtsev, B. N.; Kudryavtseva, M.V.; Сакута, Г А; Stein, G.I.

doi:10.1007/bf02915139

Cited by 144 publications

(110 citation statements)

References 14 publications

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“…Patients included in the study were of similar age (54 ± 7 years), which is important because hepatocyte ploidy varies in accordance with age (53). MS was the only risk factor for chronic liver disease (CLD) in patients with NASH (n = 16).…”

Section: Resultsmentioning

confidence: 99%

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Gentric¹,

Maillet²,

Paradis³

et al. 2015

J. Clin. Invest.

213

196

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Section: Resultsmentioning

confidence: 99%

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Gentric¹,

Maillet²,

Paradis³

et al. 2015

J. Clin. Invest.

213

196

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“…Because the diameter of diploid mouse hepatocytes averages 17 Ϯ 1 m, 29 because hepatocyte volume corresponds with ploidy, 30 and because 15%, 65%, and 20% of young adult mouse hepatocytes are diploid, tetraploid, and octoploid, respectively, 31 the result is a porto-central axis containing 9 to 10 hepatocytes. Using sophisticated graphical reconstruction, Takahashi 26 showed that the porto-central axis in human liver measured 350 to 420 m. Because diploid human hepatocytes have an average diameter of 22 to 23 m, 32 and because human hepatocytes remain diploid until the age of 50 33 the smallest functional unit in humans consists of a linear array of approximately 16 to18 hepatocytes. Similarly, the porto-central axis of rat liver consists of 13 to 15 hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Stereological measurement of porto-central gradients in gene expression in mouse liver

et al. 2004

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The liver is thought to consist of lobules, numerous repeating, randomly oriented units. Within these lobules, genes are expressed in gradients along the porto-central axis, which spans the distance between portal and central veins. We have developed a robust stereological method to map all points in an image to their position on this porto-central axis. This approach is based on the distribution of well-characterized periportal and pericentral enzymes, which are visualized on sections preceding and following the section of interest. Because expression of the model genes phosphoenolpyruvate carboxykinase and ornithine aminotransferase declines gradually with increasing distance from the portal vein and central vein, respectively, these genes can be used to prepare images with topographical information without any assumption about the shape of the hepatic unit, or about the direction or shape of the gradient to be determined. The "relative distance" image is a 2-dimensional image that accurately maps the relative position of hepatocytes on the porto-central axis in 3-dimensional space. It is superimposed on the serial section under investigation to relate local staining density to position on the porto-central axis and obtain the gene expression gradient. The method was used to determine the expression gradient of 2 periportal and 2 pericentral enzymes and their response to fasting. The "total distance" image was used to measure the length of the porto-central axis, which was approximately 210 m in mice and found to decrease 13% after 1 day of starvation. The method can be applied to any tissue component that can be stained quantitatively. (HEPATOLOGY 2004;39:343-352.)

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“…42 In normal rodents and human livers, polyploidy is a classical age-related process. 43 Of importance with respect to this, we found that in addition to a premature polyploidy, all Trim24-deficient livers at 3 months of age contained increased numbers of nuclei with intra-nuclear inclusions, 30 which is another hallmark of liver aging. 44 Furthermore, it was recently found that, in addition to proliferative phenotype of Trim24-deficient mice is dependent on Rara ligand activation, and therefore could be due to an aberrantly activated RA signaling pathway.…”

Section: Hepatocyte Polyploidization and Other Age-related Phenotypesmentioning

confidence: 90%

Trim24 (Tif1α): An essential ‘brake’ for retinoic acid-induced transcription to prevent liver cancer

Khetchoumian¹,

Teletin²,

Tisserand³

et al. 2008

Cell Cycle

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N O T D I S T R I B U T E .Retinoic acid (RA), the active derivative of vitamin A, is an important signaling molecule that controls various developmental processes and influence the proliferation and differentiation of a variety of cell types. RA exerts its biological functions primarily through binding to and activating nuclear RA receptors (RARs, which include the RARa, b and g isotypes RARA, RARB and RARC). Aberrant expression or impaired function of these nuclear receptors has been linked to diverse types of cancer. RARs are RA-dependent transcription factors that regulate gene expression through the recruitment of different co-regulators (co-activators and co-repressors). TRIM24 (formerly known as TIF1a) was among the first co-regulators identified as interacting with RARs in a ligand-dependent fashion, and it was recently shown to function in mice as a potent liver-specific tumor suppressor by attenuating Rara-mediated transcription. The fact that Trim24 -/-, but not Trim24 -/-Rara +/-, mutant mice are highly predisposed to the development of hepatocellular carcinoma (HCC) has significant implications in cancer research. This result, along with the observation that in response to pharmacological inhibition of the RA signaling, hepatocytes lacking Trim24 loose their ability to proliferate, strongly implicates Rara as a proto-oncogene in hepatocytes and demonstrates that overactivated RA signaling is deleterious to liver homeostasis.

show abstract

Human hepatocyte polyploidization kinetics in the course of life cycle

Cited by 144 publications

References 14 publications

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease

Stereological measurement of porto-central gradients in gene expression in mouse liver

Trim24 (Tif1α): An essential ‘brake’ for retinoic acid-induced transcription to prevent liver cancer

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