• Title/Summary/Keyword: transforming growth factor

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Hitological Changes on the Wound Healing Process of Alkali Burned Mouse Cornea (알칼리 화상을 입은 마우스 각막에서 상처 치유과정 중 관찰된 조직학적 변화)

  • Lee, Ji-Young;Lee, Koon-Ja
    • Journal of Korean Ophthalmic Optics Society
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    • v.13 no.4
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    • pp.161-169
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    • 2008
  • Purpose: To better understand the corneal regeneration after alkali burn regarding the initial clinical progression and the therapy, we investigated the changes of the multi factors following chemical injury in cornea. Methods: This study was performed to observation on the healing process of alkali burned cornea in aspect of immunohistochemistry by immunofluorescence or H-E staining and TUNEL assay. Results: The results showed that although a healing process occurred after alkali burn, apoptosis of epithelial, stromal and endothelial cells in the cornea was continuously observed. Neovascularization and expression of ${\alpha}$-smooth muscle actin (${\alpha}$-SMA) from limbus and from injured cornea, respectively, were observed after 3 days of alkali burn. Formation of collagen III in corneal stroma and increased expression of chondroitin sulfate are coincident with expression of ${\alpha}$-SMA and transforming growth factor-${\beta}$ (TGF-${\beta}$). Conclusions: These data suggest that medical treatment within 3 days of alkali burn will be effective to inhibit neovascularization and formation of collagen III and chondroitin sulfate. This study extends our immumohistochemical understanding of healing process in alkali burned cornea, and the results get in this study will be cornerstones in the development of therapeutic agent for accelerating renewal of chemical damaged cornea.

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Regulation of the plasminogen activator activity and inflammatory environment via transforming growth factor-beta regulation of sperm in porcine uterine epithelial cells

  • Kim, Su-jin;Cheong, Hee-Tae;Park, Choon-keun
    • Journal of Animal Reproduction and Biotechnology
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    • v.35 no.4
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    • pp.297-306
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    • 2020
  • The aims of the present study were to confirm that regulation of the PA and environment via TGF-β regulation of sperm by Percoll-separated in porcine uterine epithelial cells. And, it was performed to identify the cytokines (TGF-β1, 2 and 3, TGF-β receptor1 and 2; interleukin, IL-6, IL-8) and PA-related genes (urokinase-PA, uPA; tissue-PA, tPA; PA inhibitor, PAI; uPA-receptor, uPAR) by spermatozoa. The experiment used porcine uterus epithelial cells (pUECs) and uterine tissue epithelial cells, Boar sperm were separated by discontinuous Percoll density gradient (45/90%), and tissues were co-incubated with spermatozoa, followed by real-time PCR. PA activity was measured of sperm by discontinuous Percoll density gradient (45/90%) for 24 hours. To measure viability and acrosome damage of sperm double stained propidium iodide (PI) and SYBR-14 or FITC-PNA were used. In results, binding ratio of Percoll-separated sperm was found no differences, but sperms isolated from 90% Percoll layer reduced PA activity (p < 0.05). when co-cultured sperm selected Percoll in porcine uterus tissues epithelial cells, 90% layer sperm increased TGF-β R1, contrastively tPA and PAI-1 in comparison with control (p < 0.05). 45% sperm was decreased the expression of uPA (p < 0.05). TGF-β decreased PA activity in the supernatant collected from pUECs (p < 0.05). Especially, The group including uPA, PAI-1 were induce sperm intact, while it was reduced in sperm damage when compared to control (p < 0.05). Also, there was no significant difference group of tPA and tPA+I in the dead sperm and acrosome damage compared to control. The expression of tPA and PAI showed a common response. Percoll-separated spermatozoa in 90% layer reduced tPA and IL-related gene mRNA expression. Thus, Percoll-sparated sperm in 90% layer show that it can suppress inflammation through increased expression of TGF-β and downregulation of PA and IL in epithelial cells compared to 45% layer Percoll.

A Novel Heptapeptide that Promotes Cellular Activity and Inhibits Photoaging in Fibroblasts (섬유아세포에서 세포 활성 촉진 및 광노화 억제 효능을 보이는 신규 헵타펩타이드)

  • Lee, Eung Ji;Kang, Hana;Hwang, Bo Byeol;Chung, Yong Ji;Kim, Eun Mi
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.48 no.2
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    • pp.157-167
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    • 2022
  • In this study, we investigated the effects of heptapeptide on cellular activation and inhibition of cellular damage induced by photoaging condition in NIH3T3 fibroblasts. Cell proliferation and extracellular matrix (ECM) expression were induced by heptapeptide. The reduced cell viability under photoaging condition through ultraviolet A (UVA) irradiation was increased by heptapeptide. And UVA-induced apoptosis, matrix metalloproteinases-1 (MMP-1) expression, and reactive oxygen species (ROS) level were decreased by heptapeptide. In addition, the inhibition of transforming growth factor-β (TGF-β)/smad signaling under UVA irradiation which resulting in reduction of ECM expression was also recovered by heptapeptide. We also tested the effect of heptapeptide under another photoaging condition through heat shock, and pre-treatment of heptapeptide prevented the phosphorylation of mitogen-activated protein kinase (MAPK) and MMP-1 expression induced by heat shock. From these results, it has been shown that the heptapeptide has protective effects on fibroblasts through the up-regulation of cellular activity and through the decreasing of intracellular ROS level induced by UVA irradiation or heat shock. It is expected that the dermal protection effect of heptapeptide can be applied as a new cosmetic material in the future.

Effect of Adefovir Dipivoxil on the Inhibition of Osteogenic Differentiation of Mesenchymal Stem Cells and Osteoblasts (아데포비어가 중간엽 줄기세포와 조골세포의 골형성 분화 억제에 미치는 영향)

  • Ho PARK
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.4
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    • pp.284-290
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    • 2023
  • Adefovir dipivoxil (ADV) is used for the treatment of hepatitis and acquired immunodeficiency syndrome, but long-term use can cause osteoporosis. In this study, the effect of ADV on the osteocyte maturation process was evaluated at the level of undifferentiated cells using mesenchymal stem cells (MSCs) and osteoblasts (MG63). First, MSCs and MG63 cells were treated with ADV at different concentrations, and then a Cell Counting Kit-8 analysis was performed to determine the effect on the proliferation of each cell. Additionally, crystal violet and Hoechst staining were performed for the morphological analysis of each cell and nucleus. To determine the cause of cell hypertrophy, the transforming growth factor-beta (TGF-β) expression was investigated, and alkaline phosphatase (ALP) staining and activity were measured to determine the degree of differentiation of the MSCs and MG63 cells into mature osteocytes. The results confirmed that the ADV increases the expression of TGF-β in MSCs and MG63 cells, causing cellular and nuclear hypertrophy, and can cause osteoporosis by inhibiting cell proliferation and affecting the differentiation of mature osteocytes. Therefore, it is believed that these results can be used as a basis for understanding the adverse effects of ADV at a cytological level in basic medicine and clinical research.

Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats

  • Kim, In-Hee;Kim, Dae-Ghon;Hao, Peipei;Wang, Yunpeng;Kim, Seong-Hun;Kim, Sang-Wook;Lee, Seung-Ok;Lee, Soo-Teik
    • BMB Reports
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    • v.45 no.6
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    • pp.348-353
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    • 2012
  • L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. The present study was designed to investigate anti-fibrotic and anti-oxidative effects of OTC via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in an in vivo thioacetamide (TAA)-induced hepatic fibrosis model. Treatment with OTC (80 or 160 mg/kg) improved serum liver function parameters and significantly ameliorated liver fibrosis. The OTC treatment groups exhibited significantly lower expression of ${\alpha}$-smooth muscle actin, transforming growth factor-${\beta}1$, and collagen ${\alpha}1$ mRNA than that in the TAA model group. Furthermore, the OTC treatment groups showed a significant decrease in hepatic malondialdehyde level compared to that in the TAA model group. Nrf2 and heme oxygenase-1 expression increased significantly in the OTC treatment groups compared with that in the TAA model group. Taken together, these results suggest that OTC restores the anti-oxidative system by upregulating Nrf2; thus, ameliorating liver injury and a fibrotic reaction.

Effects of dietary supplementation of lipid-coated zinc oxide on intestinal mucosal morphology and expression of the genes associated with growth and immune function in weanling pigs

  • Song, Young Min;Kim, Myeong Hyeon;Kim, Ha Na;Jang, Insurk;Han, Jeong Hee;Fontamillas, Giselle Ann;Lee, Chul Young;Park, Byung-Chul
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.3
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    • pp.403-409
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    • 2018
  • Objective: The present study was conducted to investigate the effects of a lipid-coated zinc oxide (ZnO) supplement Shield Zn (SZ) at the sub-pharmacological concentration on intestinal morphology and gene expression in weanling pigs, with an aim to gain insights into the mechanism of actions for SZ. Methods: Forty 22-day-old weanling pigs were fed a nursery diet supplemented with 100 or 2,500 mg Zn/kg with uncoated ZnO (negative control [NC] or positive control [PC], respectively), 100, 200, or 400 mg Zn/kg with SZ for 14 days and their intestinal tissues were taken for histological and molecular biological examinations. The villus height (VH) and crypt depth (CD) of the intestinal mucosa were measured microscopically following preparation of the tissue specimen; expression of the genes associated with growth and immune function was determined using the real-time quantitative polymerase chain reaction. Results: There was no difference in daily gain, gain:feed, and diarrhea score between the SZ group and either of NC and PC. The VH and VH:CD ratio were less for the SZ group vs NC in the jejunum and duodenum, respectively (p<0.05). The jejunal mucosal mRNA levels of insulin-like growth factor (IGF-I) and interleukin (IL)-10 regressed and tended to regress (p = 0.053) on the SZ concentration with a positive coefficient, respectively, whereas the IL-6 mRNA level regressed on the SZ concentration with a negative coefficient. The mRNA levels of IGF-I, zonula occludens protein-1, tumor necrosis $factor-{\alpha}$, IL-6, and IL-10 did not differ between the SZ group and either of NC and PC; the occludin and transforming growth $factor-{\beta}1$ mRNA levels were lower for the SZ group than for PC. Conclusion: The present results are interpreted to suggest that dietary ZnO provided by SZ may play a role in intestinal mucosal growth and immune function by modulating the expression of IGF-I, IL-6, and IL-10 genes.

Functional analysis of Bombyx mori Decapentaplegic gene for bone differentiation in a mammalian cell

  • Park, Seung-Won;Goo, Tae-Won;Choi, Gwang-Ho;Kang, Seok-Woo;Kim, Sung-Wan;Kim, Seong-Ryul
    • International Journal of Industrial Entomology and Biomaterials
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    • v.27 no.1
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    • pp.159-165
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    • 2013
  • Bone morphogenetic proteins (BMPs) belong to the transforming growth factor (TGF-${\beta}$) superfamily and are involved in osteoblastic differentiation. The largest TGF-${\beta}$ superfamily subgroup shares genetic homology with human BMPs (hBMPs) and silkworm decapentaplegic (dpp). In addition, hBMPs are functionally interchangeable with Drosophila dpp. Bombyx mori dpp may induce bone formation in mammalian cells. To test this hypothesis, we synthesized the 1,285-base pairs cDNA of full-length B. mori dpp using total RNAs obtained from the fat body of 3-day-old of the $5^{th}$ instar larvae and cloned the cDNA into the pCEP4 mammalian expression vector. Next, B. mori dpp was expressed in C3H10T1/2 cells. The target cells transfected with the pCEP4-Bm dpp plasmid showed biological functions similar to those of osteogenic differentiation induction growth factors such as hBMPs. We determined the relative mRNA expression rates of Runt-related transcription factor 2 (RUNX2), osterix, osteocalcin, and alkaline phosphatase (ALP) to validate the osteoblast-specific differentiation effects of B. mori dpp by performing quantitative real-time RT-PCR. Interestingly, mRNA expression levels of the 3 marker genes except RUNX2, in cells expressing B. mori dpp were much higher than those in control cells and C3H10T1/2 cells transfected with pCEP4. These results suggested that B. mori dpp signaling regulates osterix expression during osteogenic differentiation via RUNX2-independent mechanisms.

Inhibitory Effect of 1-O-Hexyl-2,3,5-Trimethylhydroquinone on Dimethylnitrosamine-induced Liver Fibrosis in Male SD Rats

  • Jung, Yu-Ri;Lee, Young-Jung;Lee, Nam-Jin;Lin, Chun-Mai;Moon, Jun-Hawn;Chai, Hee-Yul;Kang, Jong-Koo
    • Toxicological Research
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    • v.26 no.3
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    • pp.193-201
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    • 2010
  • Hepatic fibrosis represents the main complication of most chronic liver disorders and, regardless of its etiology, is characterized by excessive deposition of extracellular matrix components. In this study, we examined that 1-O-Hexyl-2,3,5-Trimethylhydroquinone (HTHQ), a potent anti-oxidative agent, could prevent experimental hepatic fibrosis induced by dimethylnitrosamine (DMN) in male SD rats. Except for vehicle control group, other groups were induced hepatic fibrosis by intraperitoneal injection with DMN (10 mg/ml/kg) on 3 consecutive days weekly for 4 weeks. During the same 4 weeks, control and DMN groups were given vehicle and HTHQ 50, 100 and 200 groups were orally administered HTHQ (50, 100, 200 mg/kg respectively). In HTHQ 100 and 200 groups, relative liver weight and serum chemistry level improved significantly. HTHQ reduced hydroxyproline (p < 0.05) and malondialdehyde (p < 0.05) level in the liver. Histopathological examination of H&E, Masson's trichrome stain showed the reduced fibrotic septa in HTHQ 100 and 200 groups. HTHQ administration showed reduced mRNA level of PDGF (Platelet-derived growth factor), $\alpha$-SMA ($\alpha$-smooth muscle actin) and TGF-$\beta$ (transforming growth factor-$\beta$) than DMN-induced hepetic fibrosis animals in the liver tissue. In this study, we showed that HTHQ improves against DMN-induced liver fibrosis in male SD rats.

Usefullness of Mask Pack Sheets Including Marine Materials: Skin Regeneration Effect (해양소재를 이용한 마스크팩의 유용성 : 피부재생효과)

  • Park, Dae-Hwan;Park, Sang-Uk;Choi, Sung-Gon
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.45 no.2
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    • pp.167-172
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    • 2012
  • Minerals from marine materials such as deep ocean water and Dead Sea water have been used since ancient times. We made a mask pack sheet including deep ocean water and salt from the Dead Sea and evaluated the function of the mask pack sheet through animal study. Three full-thickness skin defects were made on the backs of Sprague-Dawley rats. The wounds were left untreated in group Con, and mask pack sheets including deep ocean water or deep ocean water and Dead Sea water were used as treatment for 20 min on the skin of animals in groups DP and DDP, respectively. We analyzed the gross, histological and biochemical findings. Groups DDP and DP showed decreases in wound size, as compared to group Con at 7 days after wound infliction. The histological findings revealed that wound healing had progressed further in groups DP and DDP than in group Con, with more rapid collagen deposition and regression of neutrophils. Also, the expression of vascular endothelial growth factor and transforming growth factor ${\beta}1$ were increased in groups DDP and DP compared with those in group Con at 3 days after wound infliction. Mask sheet packs including deep ocean water and Dead Sea salt affected wound healing by reducing the inflammatory phase and stimulated wound contracture by facilitating the deposition of collagen.

Hepatitis C Virus Associations with Non Hodgkin's Lymphoma: Insights on Inflammation/Angiogenesis and CD Markers

  • El-Maadawy, Eman A;Talaat, Roba M;Sadek, Rawia F;El-Sherbini, Sherif M;Abdel-Bary, Naser;Abdel-Aziz, Amal A
    • Asian Pacific Journal of Cancer Prevention
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    • v.17 no.9
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    • pp.4415-4420
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    • 2016
  • We aimed to investigate any association between hepatitis C virus (HCV) infection and non-Hodgkin's lymphoma (NHL) in the view of cytokines that control inflammation/angiogenesis and their correlation with certain CD markers. NHL patients with or without HCV infection were studied. CD5, CD30, CD3, CD20 and CD45 were immunohistochemically evaluated. Plasma levels of vascular endothelial and platelet derived growth factors (VEGF, and PDGF), tumor necrosis factor (TNF-${\alpha}$), transforming growth factor (TGF-${\beta}$), interleukin-6 (IL-6), IL-8, IL-4, IL-12 and interferon gamma (IFN-${\gamma}$) were detected by enzyme-linked immunosorbent assay (ELISA). HCV+ve NHL patients showed a significant reduction in VEGF, PDGF, IFN-${\gamma}$, CD5 and CD45 and a significant increase in IL-12 and IL-8. In conclusion, there was a significant change in cytokine secretion and expression of CD markers in HCV+ve NHL patients. Based on our results, HCV infection in NHL patients requires more in-depth investigations to explore any role in lymphoma progression.