Coordinated regulation of c-Myc and Max in rat liver development

2006 ◽  
Vol 290 (1) ◽  
pp. G145-G155 ◽  
Author(s):  
Jennifer A. Sanders ◽  
Philip A. Gruppuso
Keyword(s):  
Liver Regeneration ◽  
Fetal Development ◽  
Potential Role ◽  
Fetal Liver ◽  
Expression Patterns ◽  
Hepatocyte Proliferation ◽  
Liver Development ◽  
Adult Liver ◽  
Expression Of Genes ◽  
Growth Metabolism

The processes of liver development and regeneration involve regulation of a key network of transcription factors, the c -myc/ max/ mad network. This network regulates the expression of genes involved in hepatocyte proliferation, growth, metabolism, and differentiation. In previous studies on the expression and localization of c-Myc in the fetal and adult liver, we made the unexpected observation that c-Myc content was similar in the two. However, c-Myc was localized predominantly to the nucleolus in the adult liver. On the basis of this finding, we went on to characterize the expression patterns of the other members of the network, max and mad, comparing their regulation during late fetal development with the proliferation of mature hepatocytes that is seen in liver regeneration. We found that Max content, rather than being constitutive, as predicted by other studies, was elevated in the fetal liver compared with the adult liver. Its content correlated with hepatocyte proliferation during the perinatal transition. In contrast, mad4 expression was decreased in the fetal liver compared with the adult liver. Nucleolar localization of c-Myc coincided with changes in Max content. To explore this relationship, we overexpressed Max in cultured adult hepatocytes. High levels of Max resulted in a shift in c-Myc localization from nucleolar to diffuse nuclear. In contrast, liver regeneration was associated with an increase in c-Myc content but no change in Max content. We conclude that the regulation of Max content during liver development and its potential role in determining c-Myc localization are means by which Max may control the biological activity of the c-Myc/Max/Mad network during liver development.

scholarly journals The Expression of Human Placental Genes Related to Carotenoid/retinoid Metabolism and Pathways (P02-005-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Xiaoming Gong ◽  
Lewis Rubin
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Fetal Development ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Retinoid Metabolism ◽  
Expression Of Genes ◽  
Β Carotene

Abstract Objectives Carotenoid/retinoids status and metabolism are essential for normal placental and fetal development. Both deficiencies and excess of retinoids and some carotenoids are associated with adverse pregnancy outcomes, such as preeclampsia and preterm birth. A group of important genes involved in regulating carotenoid/retinoid metabolism and maternal to fetal transfer in human placenta. The objective of this study is to analyze (a) the expression of genes critical for regulating carotenoid/retinoid metabolism and maternal-fetal transport in human trophoblasts and (b) placental transcriptional profiles of these pathways in response to carotenoid exposure. Methods Human cytotrophoblasts (CTBs) were isolated from term placentas. CTB RNA was used to analyze the expression of genes involved in carotenoid/retinoid metabolism and pathways by qRT-PCT. First trimester-like trophoblasts (HTR-8/SVneo) were treated with either β-carotene or lycopene. RNAs were isolated and gene expression were analyzed by DNA microarrays. Results Human CTBs express retinoid metabolism and pathways-related genes, including Stra6, Lrat, Rdh5, Rdh10, Aldh1a1, Aldh1a2, Aldh1a3, Aldh8a1, Cyp26a1, and Cyp26b1, but not carotenoid metabolism genes, BCO1 and BCO2. Microarray analysis of placental gene expression profile revealed a total of 872 and 756 differentially expressed genes, respectively, compared to the control. Gene set enrichment analysis and functional annotation clustering was performed to characterize the genes differentially expressed in either β-carotene or lycopene-treated HTR-8/SVneo cells. Many known retinoid metabolism related genes and genes involved in regulation of retinoid signaling were found, and the expression profiles of these genes were markedly different in response to β-carotene treatments. Finally, the qRT-PCR and microarray analysis results showed similar gene expression patterns of carotenoid/retinoid metabolism and pathways. Conclusions These findings suggest that placental expression of genes involved in retinoid metabolism and transport in trophoblasts is critical for regulating retinoid homeostasis during placental and fetal development. Carotenoid exposure in early placental development, significantly modify the placenta gene expression related to retinoid pathways and maternal to fetal transfer. Funding Sources NIH HD421174.

Transplanted reporter cells help in defining onset of hepatocyte proliferation during the life of F344 rats

2000 ◽  
Vol 279 (3) ◽  
pp. G631-G640 ◽  
Author(s):  
Rana P. Sokhi ◽  
Pankaj Rajvanshi ◽  
Sanjeev Gupta
Keyword(s):  
Proliferative Activity ◽  
Expression Patterns ◽  
Rat Hepatocytes ◽  
Liver Parenchyma ◽  
Hepatocyte Proliferation ◽  
Liver Development ◽  
Fischer 344 ◽  
Old Rats ◽  
Cell And Gene Therapy ◽  
F344 Rats

Transplanted hepatocytes integrate in the liver parenchyma and exhibit gene expression patterns that are similar to adjacent host hepatocytes. To determine the fate of genetically marked hepatocytes in the context of hepatocellular proliferation throughout the rodent life span, we transplanted Fischer 344 (F344) rat hepatocytes into syngeneic dipeptidyl peptidase IV-deficient rats. The proliferative activity in transplanted hepatocytes was studied in animals ranging in age from a few days to 2 yr. Transplanted hepatocytes proliferated during liver development between 1 and 6 wk of age, each dividing an estimated two to five times. DNA synthesis in occasional cells was demonstrated by localizing bromodeoxyuridine incorporation. There was no evidence for transplanted cell proliferation between 6 wk and 1 yr of age. Subsequently, transplanted cells proliferated again, with increased sizes of transplanted cell clusters at 18 and 24 mo of age. The proliferative activity of transplanted cells was greater in rats entering senescence compared with during postnatal liver development. In old rats, some liver lobules were composed entirely of transplanted cells. We conclude that hepatocyte proliferation in the livers of very young and old F344 rats is regulated in a temporally determined, biphasic manner. The findings will be relevant to mechanisms concerning liver development, senescence, and oncogenesis, as well as to cell and gene therapy.

Promoter-specific IGF2 imprinting status and its plasticity during human liver development

Development ◽  
1995 ◽  
Vol 121 (2) ◽  
pp. 309-316 ◽  
Author(s):  
T.J. Ekstrom ◽  
H. Cui ◽  
X. Li ◽  
R. Ohlsson
Keyword(s):  
Postnatal Development ◽  
Human Liver ◽  
Expression Patterns ◽  
Liver Development ◽  
Maternal Allele ◽  
Adult Liver ◽  
Biallelic Expression ◽  
Prenatal And Postnatal Development

IGF2 has been shown to be expressed preferentially from the paternally derived allele, although the maternal allele can be found active during both prenatal and postnatal development as well as in neoplastic tumours in humans. We addressed here whether or not the biallelic expression patterns that can be seen during postnatal human liver development reflected a coordinated change in the activities of the four promoters of human IGF2. We show here that the P2, P3 and P4 promoters, but not the P1 promoter, display monoallelic activity in embryonic, neonatal and younger infant liver specimens. The P2, P3 and P4 promoters can, however, be found active either monoallelically or biallelically or even monoallelically on opposite parental alleles in older infant and adult liver specimens. In contrast, H19, which is closely linked to IGF2, is monoallelically expressed in all postnatal liver samples analysed. We conclude that the functional imprinting status of IGF2 during postnatal liver development appears to be promoter/enhancer-specific and either partly or completely independent of H19.

scholarly journals IL-22 is involved in liver regeneration after hepatectomy

2010 ◽  
Vol 298 (1) ◽  
pp. G74-G80 ◽  
Author(s):  
Xiaodan Ren ◽  
Bin Hu ◽  
Lisa M. Colletti
Keyword(s):  
Liver Regeneration ◽  
General Anesthesia ◽  
Partial Hepatectomy ◽  
Potential Role ◽  
Cellular Proliferation ◽  
Cell Types ◽  
In Vitro Studies ◽  
Hepatocyte Proliferation

Hepatocyte proliferation following partial hepatectomy is an important component of liver regeneration, and recent in vitro studies have shown that IL-22 is involved in cellular proliferation in a variety of cell types, including hepatocytes. IL-22 functions through IL-10Rβ and IL-22Rα. The goal of this study was to investigate the potential role of IL-22 in liver regeneration after 70% hepatectomy. Following 70% hepatectomy, done under general anesthesia in mice, serum IL-22 and hepatic IL-22Rα mRNA were significantly increased. Although administration of exogenous IL-22 prior to hepatectomy did not increase hepatocyte proliferation, administration of anti-IL-22 antibody before hepatectomy did significantly decrease hepatocyte proliferation. Furthermore, IL-22 treatment prior to 70% hepatectomy induced stat-3 activation; no significant changes were seen in ERK1/2 activation, stat-1 activation, or stat-5 activation. IL-22 pretreatment also significantly increased hepatic and serum IL-6 levels. In addition, animals treated with anti-IL-22 antibody also expressed less TGF-α. In conclusion, these data suggest that IL-22 is involved in liver regeneration and this may be due to interaction with IL-6 and TGF-α cascades.

Gene expression analysis identifies novel genes participating in early murine liver development and adult liver regeneration

2006 ◽  
Vol 74 (4) ◽  
pp. 167-173 ◽  
Author(s):  
Andrea Jochheim-Richter ◽  
Urda Rüdrich ◽  
Dirk Koczan ◽  
Tina Hillemann ◽  
Simon Tewes ◽  
...  
Keyword(s):  
Gene Expression ◽  
Liver Regeneration ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Liver Development ◽  
Adult Liver ◽  
Novel Genes ◽  
Murine Liver

scholarly journals A study on histology of fetal liver

2015 ◽  
Vol 04 (01) ◽  
pp. 026-029
Author(s):  
Jaiswal A. ◽  
Sinha DN ◽  
Singh AK
Keyword(s):  
Kupffer Cells ◽  
Fetal Development ◽  
Special Function ◽  
Fetal Liver ◽  
Fetal Life ◽  
Human Fetuses ◽  
Histological Findings ◽  
Adult Liver ◽  
Normal Human ◽  
Insight Into

Abstract Background and aims : Background and aims : The liver during fetogenesis does not follow classical lobular pattern. Normal histology of the fetal liver at various stages of development was studied to get insight into the morphology of fetal liver and special function it performs in fetal life. Method: Dissection of 29 normal human fetuses was done and histological findings of liver were noted with respect to the age of fetus. The histology of fetal liver was studied using H & E stain and important features of fetal liver were studied. Result: Fetal liver histology is different from adult liver. Unlike adult liver, fetal liver shows hepatocytes arranged in sheets predominantly with cordlike pattern at places. The sinusoids are dilated and filled with hemopoietic cells, which could be appreciated at different stages of fetal development. The Kupffer cells were also noticed in fetal liver. Conclusion: The present study will be helpful in understanding the normal histology of fetal liver and add to the existing knowledge regarding development of fetal liver.

378: 14-3-3 Expression Patterns in the Human Kidney: From Fetal Development to the Adult State to Malignant Transformation

2005 ◽  
Vol 173 (4S) ◽  
pp. 103-103
Author(s):  
Adam G. Baseman ◽  
Andrew J. Kirsch ◽  
Fray F. Marshall ◽  
Haiyen E. Zhau ◽  
Leland W.K. Chung ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Fetal Development ◽  
Expression Patterns ◽  
Human Kidney

scholarly journals F4/80+ Kupffer Cell-Derived Oncostatin M Sustains the Progression Phase of Liver Regeneration through Inhibition of TGF-β2 Pathway

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2231
Author(s):  
Qingjun Lu ◽  
Hao Shen ◽  
Han Yu ◽  
Jing Fu ◽  
Hui Dong ◽  
...  
Keyword(s):  
Liver Regeneration ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Regenerative Process ◽  
Oncostatin M ◽  
Hepatocyte Proliferation ◽  
Initiation Phase ◽  
Distinct Role

The role of Kupffer cells (KCs) in liver regeneration is complicated and controversial. To investigate the distinct role of F4/80+ KCs at the different stages of the regeneration process, two-thirds partial hepatectomy (PHx) was performed in mice to induce physiological liver regeneration. In pre- or post-PHx, the clearance of KCs by intraperitoneal injection of the anti-F4/80 antibody (α-F4/80) was performed to study the distinct role of F4/80+ KCs during the regenerative process. In RNA sequencing of isolated F4/80+ KCs, the initiation phase was compared with the progression phase. Immunohistochemistry and immunofluorescence staining of Ki67, HNF-4α, CD-31, and F4/80 and Western blot of the TGF-β2 pathway were performed. Depletion of F4/80+ KCs in pre-PHx delayed the peak of hepatocyte proliferation from 48 h to 120 h, whereas depletion in post-PHx unexpectedly led to persistent inhibition of hepatocyte proliferation, indicating the distinct role of F4/80+ KCs in the initiation and progression phases of liver regeneration. F4/80+ KC depletion in post-PHx could significantly increase TGF-β2 serum levels, while TGF-βRI partially rescued the impaired proliferation of hepatocytes. Additionally, F4/80+ KC depletion in post-PHx significantly lowered the expression of oncostatin M (OSM), a key downstream mediator of interleukin-6, which is required for hepatocyte proliferation during liver regeneration. In vivo, recombinant OSM (r-OSM) treatment alleviated the inhibitory effect of α-F4/80 on the regenerative progression. Collectively, F4/80+ KCs release OSM to inhibit TGF-β2 activation, sustaining hepatocyte proliferation by releasing a proliferative brake.

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