• Journal of Animal Science and Technology
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• v.63 no.4
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• pp.934-953
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• 2021

Ciglitazone is a member of the thiazolidinedione family, and specifically binds to peroxisome proliferator-activated receptor-γ (PPARγ), thereby promoting adipocyte differentiation. We hypothesized that ciglitazone as a PPARγ ligand in the absence of an adipocyte differentiation cocktail would increase adiponectin and adipogenic gene expression in bovine satellite cells (BSC). Muscle-derived BSCs were isolated from six, 18-month-old Yanbian Yellow Cattle. The BSC were cultured for 96 h in differentiation medium containing 5 µM ciglitazone (CL), 10 µM ciglitazone (CM), or 20 µM ciglitazone (CH). Control (CON) BSC were cultured only in a differentiation medium (containing 2% horse serum). The presence of myogenin, desmin, and paired box 7 (Pax7) proteins was confirmed in the BSC by immunofluorescence staining. The CL, CM, and CH treatments produced higher concentrations of triacylglycerol and lipid droplet accumulation in myotubes than those of the CON treatment. Ciglitazone treatments significantly increased the relative expression of PPARγ, CCAAT/enhancer-binding protein alpha (C/EBPα), C/EBPβ, fatty acid synthase, stearoyl-CoA desaturase, and perilipin 2. Ciglitazone treatments increased gene expression of Pax3 and Pax7 and decreased expression of myogenic differentiation-1, myogenin, myogenic regulatory factor-5, and myogenin-4 (p < 0.01). Adiponectin concentration caused by ciglitazone treatments was significantly greater than CON (p < 0.01). RNA sequencing showed that 281 differentially expressed genes (DEGs) were found in the treatments of ciglitazone. DEGs gene ontology (GO) analysis showed that the top 10 GO enrichment significantly changed the biological processes such as protein trimerization, negative regulation of cell proliferation, adipocytes differentiation, and cellular response to external stimulus. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that DEGs were involved in the p53 signaling pathway, PPAR signaling pathway, biosynthesis of amino acids, tumor necrosis factor signaling pathway, non-alcoholic fatty liver disease, PI3K-Akt signaling pathway, and Wnt signaling pathway. These results indicate that ciglitazone acts as PPARγ agonist, effectively increases the adiponectin concentration and adipogenic gene expression, and stimulates the conversion of BSC to adipocyte-like cells in the absence of adipocyte differentiation cocktail.

• Journal of Food Hygiene and Safety
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• v.21 no.3
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• pp.171-180
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• 2006

Peroxisome proliferatorr-activated receptor-gamma $(PPAR{\gamma})$ must form a heterodimer with the retinoid-X receptor (RXR) to bind DNA, and its transcriptional activity is thought to be maximized by ligands specific for either receptor. Activated $(PPAR{\gamma})$ and $(PPAR{\gamma})$ ligands may influence tumor growth through regulation of the tumor suppressor PTEN. Our aim in this study was to determine whether co-stimulation with the $(PPAR{\gamma})$ ligand, ciglitazone, and RXR ligand can synergistically upregulate PTEN in human acute promyelocytic leukemia (APL) cells and consequently potentate the inhibition of cell growth and cell cycle progression of these cells. Human leukemia cell line, HL-60 cells were exposed to all-trans-retinol and ciglutazone. The PTEN expression was measured as the level of PTEN mRNA expression by RT-PCR and as the level of PTEN expression by western blot analysis. Cell cycle analysis was carried out by a propidium iodide (PI) staining method and analyzed with a FACScan. The $(PPAR{\gamma})$ ligand, ciglitazone, and the RXR ligand, retinoic acid, upregulated PTEN expression by HL-60 cells in time- and dose-dependent manners, respectively. This was significantly enhanced by a combination of both ciglitazone and retinoic acid. Moreover, these compounds synergistically induced arrests of both cell growth and the $G_l$ phase of the cell cycle. Thus, the activation of the $(PPAR{\gamma})$:RXR heterodimer may represent a regulatory pathway for human leukemia cells and there may be important roles for $(PPAR{\gamma})$ and RXR ligands in prophylactic and therapeutic approaches fur controlling leukemia through the upregulation of PTEN.

• Biomolecules & Therapeutics
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• v.23 no.1
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• pp.71-76
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• 2015

Peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$) was identified as a cell-intrinsic regulator of Th17 cell differentiation. Th17 cells have been associated with several autoimmune diseases, including experimental autoimmune encephalomyelitis (EAE), inflammatory bowel disease (IBD), and collagen-induced arthritis. In this study, we confirmed $PPAR{\gamma}$-mediated inhibition of Th17 cell differentiation and cytokine production at an early stage. Treatment with ciglitazone, a $PPAR{\gamma}$ ligand, reduced both IL-$1{\beta}$-mediated enhancement of Th17 differentiation and activation of Th17 cells after polarization. For Th17 cell differentiation, we found that ciglitazone-treated cells had a relatively low proliferative activity and produced a lower amount of cytokines, regardless of the presence of IL-$1{\beta}$. The inhibitory activity of ciglitazone might be due to decrease of CCNB1 expression, which regulates the cell cycle in T cells. Hence, we postulate that a pharmaceutical $PPAR{\gamma}$ activator might be a potent candidate for treatment of Th17-mediated autoimmune disease patients.

• Journal of Periodontal and Implant Science
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• v.35 no.1
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• pp.133-152
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• 2005

1. 목적 Prostaglandin은 치주질환과 관련된 국소적 골 대사에 중요한 역할을 한다. ${\Delta}^{12}PGJ_2$는 생체 내에서 혈장의 존재 하에 형성되는 천연 $PGD_2$ 대사산물이며 peroxisome- proliferator에 의해 활성화되는 감마 수용체 (PPAR ${\Gamma}$)에 대해 높은 친화성을 갖는 리간드로서 핵 수용체군에 속하는 전사조절인자이다. 이 연구의 목적은 골화 과정에서 ${\Delta}^{12}PGJ_2$의 역할을 규명하기 위해, 조골세포주의 증식과 분화에 미치는 영향과 그에 관련된 세포기전을 조사하는 데에 있다. 2. 방법 인간 골육종세포주인 Saos-2 (ATCC.HTB 85)와 쥐의 조골세포주 (MC3T3-E1)를 배양한 후 실험군에 농도가 각각 $10^{-5}$, $10^{-6}$, $10^{-7}$, $10^{-8}$, $10^{-9}$ 몰인 ${\Delta}^{12}PGJ_2$와 ciglitazone (합성 PPAR 감마 길항체)를 첨가하였다. 조골세포에서 PPAR 감마의 발현을 관찰하기 위해 역전사효소-중합효소연쇄반응(RT-PCR)을 특정한 primer를 이용하여 시행하였다. 세포 증식은 1일, 2일, 3 일째에 MIT 분석법으로 측정하였고, 2 일째에 알칼리성 인산효소 (ALPase) 생산을 측정하였다. 위의 결과에서 얻은 적정한 농도에서 다양한 조골세포 분화의 표지자들-제 1 형 교원질, 알칼리성 인산효소, osteopontin 및 bone sialoprotein-에 대한 간이 정량적 역전사효소-중합효소연쇄반응 (semiquantitative RT-PCR)을 실시하였으며 골결절 형성에 대한 효과를 알아보고자 석회화 분석도 시행하였다. 3. 결과 ${\Delta}^{12}PGJ_2$와 ciglitazone 모두 Saos-2 세포주의 증식을 촉진시켰다 .$10^{-8}$ 몰의 ${\Delta}^{12}PGJ_2$와 $10^{-6}$몰의 ciglitazone을 첨가한 실험군을 대조군과 비교했을 때, 시간에 비례하여 세포 증식률이 증가되었다. 알칼리성 인산효소의 활성화 검사에서도 증식률에서와 유사한 결과를 보여주었다. 간이 정량적 RT-PCR에서는 ${\Delta}^{12}PGJ_2$로 처리한 군의 경우 제 1 형 교원질, 알칼리성 인산효소, osteopontin, 그리고 bone sialoprotein의 상대적 mRNA 수준이 유의하게 높았다. 석회화 분석에서는 MC3T3-E1 세포를 $10^{-6}$ 몰의 ${\Delta}^{12}PGJ_2$로 처리한 군과 $10^{-5}$ 몰의 ciglitazone으로 처리한 군에서 현저한 골결절 형성을 보였다. 이러한 결과들은 ${\Delta}^{12}PGJ_2$가 유용한 골 유도물질이 될 수 있으며 또한 그 작용기전이 PPAR 감마-의존형 경로와 연관되어 있음을 보여준다.

• YAKHAK HOEJI
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• v.54 no.2
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• pp.91-96
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• 2010

Berberine, an isoquinoline alkaloid, has a wide range of pharmacological effects, including anti-inflammation. It has been reported that berberine inhibits experimental colitis through inhibition of IL-8, and that inhibitory effect of berberine on inflammatory cytokine expression is mediated through peroxisome proliferator activated receptor (PPAR)-$\gamma$. In this study, we examined the effects and action mechanism of berberine on the tumor necrosis factor (TNF)-$\alpha$-induced monocyte adhesion to HT29 human colonic epithelial cells, which is commonly used as an in vitro model of inflammatory bowel disease (IBD). Berberine significantly inhibited the TNF-$\alpha$-induced monocyte adhesion to HT29, which is similar to the effect of PDTC, a nuclear factor (NF)-$\kappa$B inhibitor. However, ciglitazone and GW, the ligands of PPAR-$\gamma$, did not suppress the TNF-$\alpha$-induced monocyte adhesion to HT29 cells. In addition, TNF-$\alpha$-induced chemokine expression and NF-$\kappa$B transcriptional activity were significantly inhibited by berberine in a concentration-dependent manner. The results suggest that inhibitory effect of berberine on colitis is mediated through suppression of NF-$\kappa$B and NF-$\kappa$B-dependent chemokine expression.