scholarly journals Astragaloside IV Suppresses Hepatic Proliferation in Regenerating Rat Liver after 70% Partial Hepatectomy via Down-Regulation of Cell Cycle Pathway and DNA Replication

Molecules ◽  
2021 ◽  
Vol 26 (10) ◽  
pp. 2895
Author(s):  
Gyeong-Seok Lee ◽  
Hee-Yeon Jeong ◽  
Hyeon-Gung Yang ◽  
Young-Ran Seo ◽  
Eui-Gil Jung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Dna Replication ◽  
Growth Factor ◽  
Partial Hepatectomy ◽  
Growth Regulation ◽  
Transforming Growth Factor ◽  
Mapk Signaling ◽  
Regenerating Liver ◽  
Astragaloside Iv ◽  
Cell Cycle Pathway

Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor β1 (TGFβ1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.

Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function

1991 ◽  
Vol 11 (10) ◽  
pp. 4952-4958
Author(s):  
A Zentella ◽  
F M Weis ◽  
D A Ralph ◽  
M Laiho ◽  
J Massagué
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Early Gene ◽  
Tgf Beta ◽  
Suppressive Function ◽  
Growth Factor Beta ◽  
Pai 1

The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth-suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth-suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB.

scholarly journals The Activity of Differentiation Factors Induces Apoptosis in Polyomavirus Large T-Expressing Myoblasts

1998 ◽  
Vol 9 (6) ◽  
pp. 1449-1463 ◽  
Author(s):  
Gian Maria Fimia ◽  
Vanesa Gottifredi ◽  
Barbara Bellei ◽  
Maria Rosaria Ricciardi ◽  
Agostino Tafuri ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Growth Factor ◽  
Cell Cycle Progression ◽  
Transforming Growth Factor ◽  
Myogenic Differentiation ◽  
Transforming Growth Factor Β ◽  
Large Tumor ◽  
Cycle Progression

It is commonly accepted that pathways that regulate proliferation/differentiation processes, if altered in their normal interplay, can lead to the induction of programmed cell death. In a previous work we reported that Polyoma virus Large Tumor antigen (PyLT) interferes with in vitro terminal differentiation of skeletal myoblasts by binding and inactivating the retinoblastoma antioncogene product. This inhibition occurs after the activation of some early steps of the myogenic program. In the present work we report that myoblasts expressing wild-type PyLT, when subjected to differentiation stimuli, undergo cell death and that this cell death can be defined as apoptosis. Apoptosis in PyLT-expressing myoblasts starts after growth factors removal, is promoted by cell confluence, and is temporally correlated with the expression of early markers of myogenic differentiation. The block of the initial events of myogenesis by transforming growth factor β or basic fibroblast growth factor prevents PyLT-induced apoptosis, while the acceleration of this process by the overexpression of the muscle-regulatory factor MyoD further increases cell death in this system. MyoD can induce PyLT-expressing myoblasts to accumulate RB, p21, and muscle- specific genes but is unable to induce G00arrest. Several markers of different phases of the cell cycle, such as cyclin A, cdk-2, and cdc-2, fail to be down-regulated, indicating the occurrence of cell cycle progression. It has been frequently suggested that apoptosis can result from an unbalanced cell cycle progression in the presence of a contrasting signal, such as growth factor deprivation. Our data involve differentiation pathways, as a further contrasting signal, in the generation of this conflict during myoblast cell apoptosis.

scholarly journals Pregnancy facilitates maternal liver regeneration after partial hepatectomy

2020 ◽  
Vol 318 (4) ◽  
pp. G772-G780
Author(s):  
Joonyong Lee ◽  
Veronica Garcia ◽  
Shashank Manohar Nambiar ◽  
Huaizhou Jiang ◽  
Guoli Dai
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Liver Resection ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Liver Fat ◽  
Fat Accumulation ◽  
Positive Effects ◽  
Maternal Liver ◽  
Hepatic Fat

Liver resection induces robust liver regrowth or regeneration to compensate for the lost tissue mass. In a clinical setting, pregnant women may need liver resection without terminating pregnancy in some cases. However, how pregnancy affects maternal liver regeneration remains elusive. We performed 70% partial hepatectomy (PH) in nonpregnant mice and gestation day 14 mice, and histologically and molecularly compared their liver regrowth during the next 4 days. We found that compared with the nonpregnant state, pregnancy altered the molecular programs driving hepatocyte replication, indicated by enhanced activities of epidermal growth factor receptor and STAT5A, reduced activities of cMet and p70S6K, decreased production of IL-6, TNFα, and hepatocyte growth factor, suppressed cyclin D1 expression, increased cyclin A1 expression, and early activated cyclin A2 expression. As a result, pregnancy allowed the remnant hepatocytes to enter the cell cycle at least 12 h earlier, increased hepatic fat accumulation, and enhanced hepatocyte mitosis. Consequently, pregnancy ameliorated maternal liver regeneration following PH. In addition, a report showed that maternal liver regrowth after PH is driven mainly by hepatocyte hypertrophy rather than hyperplasia during the second half of gestation in young adult mice. In contrast, we demonstrate that maternal liver relies mainly on hepatocyte hyperplasia instead of hypertrophy to restore the lost mass after PH. Overall, we demonstrate that pregnancy facilitates maternal liver regeneration likely via triggering an early onset of hepatocyte replication, accumulating excessive liver fat, and promoting hepatocyte mitosis. The results from our current studies enable us to gain more insights into how maternal liver regeneration progresses during gestation. NEW & NOTEWORTHY We demonstrate that pregnancy may generate positive effects on maternal liver regeneration following partial hepatectomy, which are manifested by early entry of the cell cycle of remnant hepatocytes, increased hepatic fat accumulation, enhanced hepatocyte mitosis, and overall accelerated liver regrowth.

scholarly journals Early gene responses to transforming growth factor-beta in cells lacking growth-suppressive RB function.

1991 ◽  
Vol 11 (10) ◽  
pp. 4952-4958 ◽  
Author(s):  
A Zentella ◽  
F M Weis ◽  
D A Ralph ◽  
M Laiho ◽  
J Massagué
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Lung Epithelial Cells ◽  
Early Gene ◽  
Tgf Beta ◽  
Suppressive Function ◽  
Growth Factor Beta ◽  
Pai 1

The growth-suppressive function of the retinoblastoma susceptibility gene product, RB, has been implicated in the mediation of growth inhibition and negative regulation of certain proliferation related genes by transforming growth factor-beta 1 (TGF-beta 1). Early gene responses to TGF-beta 1 were examined in order to determine their dependence on the cell cycle and on the growth-suppressive function of RB. TGF-beta 1, which rapidly elevates the steady-state level of junB and PAI-1 mRNAs and decreases that of c-myc mRNA, induces these responses in S-phase populations of Mv1Lu lung epithelial cells containing RB in a phosphorylated state. Since in this state RB is presumed to lack growth-suppressive activity, the response to TGF-beta 1 was also examined in DU145 human prostate carcinoma cells whose mutant RB product lacks growth-suppressive function. In these cells, TGF-beta 1 also decreases c-myc expression at the transcription initiation level. These results suggests that the c-myc, junB, and PAI-1 responses to TGF-beta 1 are not restricted to the G1 phase of the cell cycle and that down-regulation of c-myc expression by TGF-beta 1 can occur through a mechanism independent from the growth-suppressive function of RB.

scholarly journals Mediation of the inhibitory effect of thyroid hormone on proliferation of hepatoma cells by transforming growth factor-beta

2006 ◽  
Vol 36 (1) ◽  
pp. 9-21 ◽  
Author(s):  
Chun-Che Yen ◽  
Ya-Hui Huang ◽  
Chu-Yu Liao ◽  
Cheng-Jung Liao ◽  
Wan-Li Cheng ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Thyroid Hormone ◽  
Cell Growth ◽  
Growth Inhibition ◽  
Transforming Growth Factor ◽  
Cyclin E ◽  
Hepatoma Cell ◽  
Stable Cell Line ◽  
Mrna Levels

Thyroid hormone (triiodothyronine, T3) regulates growth, development and differentiation. To examine the influence of T3 on hepatoma cell growth, thyroid receptor (TR)α1 or TRβ1 over-expressing HepG2 cell lines were used. Growth of the HepG2-TR stable cell line was inhibited by over 50% following treatment with T3. However, transforming growth factor (TGF)-β neutralizing antibody, but not the control antibody can reverse the cell growth inhibition effect of T3. Flow cytometric analysis indicated that the growth inhibition was apparent at the transition point between the G1 and S phases of the cell cycle. The expression of major cell cycle regulators was used to provide further evidence for the growth inhibition. Cyclin-dependent kinase 2 (cdk2) and cyclin E were down-regulated in HepG2-TR cells. Moreover, p21 protein or mRNA levels were up-regulated by around 5-fold or 7.3-fold respectively following T3 treatment. Furthermore, phospho-retinoblastoma (ppRb) protein was down-regulated by T3. The expression of TGF-β was studied to delineate the repression mechanism. TGF-β was stimulated by T3 and its promoter activity was enhanced six- to eight-fold by T3. Furthermore, both T3 and TGF-β repressed the expression of cdk2, cyclin E and ppRb. On the other hand, TGF-β neutralizing but not control antibody blocked the repression of cdk2, cyclin E and ppRb by T3. These results demonstrated that T3 might play a key role in liver tumor cell proliferation.

scholarly journals FOXO1 transcription factor regulates chondrogenic differentiation through transforming growth factor β1 signaling

2019 ◽  
Vol 294 (46) ◽  
pp. 17555-17569 ◽  
Author(s):  
Ichiro Kurakazu ◽  
Yukio Akasaki ◽  
Mitsumasa Hayashida ◽  
Hidetoshi Tsushima ◽  
Norio Goto ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Growth Factor ◽  
Cell Cycle Arrest ◽  
Chondrogenic Differentiation ◽  
Transforming Growth Factor ◽  
Human Mesenchymal Stem Cells ◽  
Type Ii Collagen ◽  
Transforming Growth Factor Β1 ◽  
Type Ii ◽  
Cycle Arrest

The forkhead box O (FOXO) proteins are transcription factors involved in the differentiation of many cell types. Type II collagen (Col2) Cre-Foxo1-knockout and Col2-Cre-Foxo1,3,4 triple-knockout mice exhibit growth plate malformation. Moreover, recent studies have reported that in some cells, the expressions and activities of FOXOs are promoted by transforming growth factor β1 (TGFβ1), a growth factor playing a key role in chondrogenic differentiation. Here, using a murine chondrogenic cell line (ATDC5), mouse embryos, and human mesenchymal stem cells, we report the mechanisms by which FOXOs affect chondrogenic differentiation. FOXO1 expression increased along with chondrogenic differentiation, and FOXO1 inhibition suppressed chondrogenic differentiation. TGFβ1/SMAD signaling promoted expression and activity of FOXO1. In ATDC5, FOXO1 knockdown suppressed expression of sex-determining region Y box 9 (Sox9), a master regulator of chondrogenic differentiation, resulting in decreased collagen type II α1 (Col2a1) and aggrecan (Acan) expression after TGFβ1 treatment. On the other hand, chemical FOXO1 inhibition suppressed Col2a1 and Acan expression without suppressing Sox9. To investigate the effects of FOXO1 on chondrogenic differentiation independently of SOX9, we examined FOXO1's effects on the cell cycle. FOXO1 inhibition suppressed expression of p21 and cell-cycle arrest in G0/G1 phase. Conversely, FOXO1 overexpression promoted expression of p21 and cell-cycle arrest. FOXO1 inhibition suppressed expression of nascent p21 RNA by TGFβ1, and FOXO1 bound the p21 promoter. p21 inhibition suppressed expression of Col2a1 and Acan during chondrogenic differentiation. These results suggest that FOXO1 is necessary for not only SOX9 expression, but also cell-cycle arrest during chondrogenic differentiation via TGFβ1 signaling.

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