• Title/Summary/Keyword: hepatocyte growth factor (HGF)

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Transforming Growth Factor-$\beta$ is a Possible Paracrine Mediator in the Human Endometrial Decidualization (인간자궁내막의 탈락막화 (Decudualization)에 있어서 TGF-$\beta$ (Transforming Growth Factor-$\beta$)의 역할)

  • Park, Dong-Wook;Choi, Dong-Soon;Kim, Mi-Ran;Hwang, Kyung-Joo;Jo, Mi-Yeong;Ahn, Seong-Hee;Min, Churl-K.;Ryu, Hee-Sug
    • Clinical and Experimental Reproductive Medicine
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    • v.30 no.1
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    • pp.65-75
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    • 2003
  • Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.

No-Touch Radiofrequency Ablation of VX2 Hepatic Tumors In Vivo in Rabbits: A Proof of Concept Study

  • Kim, Tae-Hyung;Choi, Hyoung In;Kim, Bo Ram;Kang, Ji Hee;Nam, Ju Gang;Park, Sae Jin;Lee, Seunghyun;Yoon, Jeong Hee;Lee, Dong Ho;Joo, Ijin;Lee, Jeong Min
    • Korean Journal of Radiology
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    • v.19 no.6
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    • pp.1099-1109
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    • 2018
  • Objective: In a proof of concept study, we compared no-touch radiofrequency ablation (NtRFA) in bipolar mode with conventional direct tumor puncture (DTP) in terms of local tumor control (LTC), peritoneal seeding, and tumorigenic factors, in the rabbit VX2 subcapsular hepatic tumor model. Materials and Methods: Sixty-two rabbits with VX2 subcapsular hepatic tumors were divided into three groups according to the procedure: DTP-RFA (n = 25); NtRFA (n = 25); and control (n = 12). Each of the three groups was subdivided into two sets for pathologic analysis (n = 24) or computed tomography (CT) follow-up for 6 weeks after RFA (n = 38). Ultrasonography-guided DTP-RFA and NtRFA were performed nine days after tumor implantation. LTC was defined by either achievement of complete tumor necrosis on histopathology or absence of local tumor progression on follow-up CT and autopsy. Development of peritoneal seeding was also compared among the groups. Serum hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) were measured via ELISA (Elabscience Biotechnology Co.) after RFA for tumorigenic factor evaluation. Results: Regarding LTC, there was a trend in NtRFA (80%, 20/25) toward better ablation than in DTP-RFA (56%, 14/25) (p = 0.069). Complete tumor necrosis was achieved in 54.5% of DTP-RFA (6/11) and 90.9% of NtRFA (10/11). Peritoneal seeding was significantly more common in DTP-RFA (71.4%, 10/14) than in NtRFA (21.4%, 3/14) (p = 0.021) or control (0%). Elevations of HGF, VEGF or IL-6 were not detected in any group. Conclusion: No-touch radiofrequency ablation led to lower rates of peritoneal seeding and showed a tendency toward better LTC than DTP-RFA.

Analysis of (-)-Epigallocatechin-3-Gallate-Induced Apoptosis and Inhibition of Invasiveness in Oral Cavity Carcinoma Squamous Cell Carcinoma According to Expression of c-Met (구강암편평세포암에서 c-Met 발현여부에 따른 (-)-Epigallocatechin-3-Gallate의 세포사멸 및 종양침습억제효과의 변화분석)

  • Shin, Yoo-Seob;Koh, Yoon-Woo;Choi, Eun-Chang;Kang, Sung-Un;Hwang, Hye-Sook;Choo, Oak-Sung;Lee, Han-Bin;Kim, Chul-Ho
    • Korean Journal of Head & Neck Oncology
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    • v.27 no.1
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    • pp.3-11
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    • 2011
  • Hepatocyte growth factor(HGF) and c-Met play an important role in the control of tumor growth and invasion, and they are known to be good prognostic indicators of patient outcome. Epigallocatechin-3-gallate (EGCG) has been shown to have chemopreventive and therapeutic properties by modulating multiple signal pathways regarding the control of proliferation and invasion of cells. In this study, we evaluated the role of c-Met in EGCG-induced inhibition of invasion and apoptosis in an oral cancer cell line. In KB cells where c-Met was knocked down with siRNA, we performed invasion assay and FACS with Annexin V-FITC/PT staining. In addition, we checked the change of mitochondrial membrane potential(MMP) and the generation of reactive oxygen species(ROS). EGCG-induced inhibition of invasiveness was significantly decreased after the knock-down of c-Met. EGCG-induced apoptosis, MMP change and ROS generation was also reduced in c-Met knock-ed-down KB cells. These results suggest that c-Met is involved in EGCG-induced apoptosis and inhibition of invasiveness of oral cancer cell line.

Met inactivation by S-allylcysteine suppresses the migration and invasion of nasopharyngeal cancer cells induced by hepatocyte growth factor

  • Cho, Oyeon;Hwang, Hye-Sook;Lee, Bok-Soon;Oh, Young-Taek;Kim, Chul-Ho;Chun, Mison
    • Radiation Oncology Journal
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    • v.33 no.4
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    • pp.328-336
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    • 2015
  • Purpose: Past studies have reported that S-allylcysteine (SAC) inhibits the migration and invasion of cancer cells through the restoration of E-cadherin, the reduction of matrix metalloproteinase (MMP) and Slug protein expression, and inhibition of the production of reactive oxygen species (ROS). Furthermore, evidence is emerging that shows that ROS induced by radiation could increase Met activation. Following on these reports of SAC and Met, we investigated whether SAC could suppress Met activation. Materials and Methods: Wound healing, invasion, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium (MTT), soft agar colony forming, western blotting, and gelatin zymography assays were performed in the human nasopharyngeal cancer cell lines HNE1 and HONE1 treated with SAC (0, 10, 20, or 40 mM) and hepatocyte growth factor (HGF). Results: This study showed that SAC could suppress the migration and invasion of HNE1 and HONE1 cell lines by inhibiting p-Met. An increase of migration and invasion induced by HGF and its decrease in a dose dependent manner by SAC in wound healing and invasion assays was observed. The reduction of p-Met by SAC was positively correlated with p-focal adhesion kinase (p-FAK) and p-extracellular related kinase (p-ERK in both cell lines). SAC reduced Slug, MMP2, and MMP9 involved in migration and invasion with the inhibition of Met-FAK signaling. Conclusion: These results suggest that SAC inhibited not only Met activation but also the downstream FAK, Slug, and MMP expression. Finally, SAC may be a potent anticancer compound for nasopharyngeal cancer treated with radiotherapy.

Novel Heptapeptide Binds to the Lgr5 Induces Activation of Human Hair Follicle Cells and Differentiation of Human Hair Follicle Bulge Stem Cells (Lgr5와 결합하는 신규 헵타펩타이드를 이용한 인체 모낭 세포의 활성과 모낭줄기세포 분화 유도)

  • Min Woong Kim;Eung Ji Lee;Ha-Na Gil;Yong Ji Chung;Eun Mi Kim
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.49 no.1
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    • pp.75-85
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    • 2023
  • This study was conducted to assess the effect of heptapeptide, composed of seven amino acids, on the activation of human hair cells isolated from human hair follicles. We have confirmed that the heptapeptide could bind to Lgr5 from the results of surface plasmon resonance (SPR) analysis. Heptapeptide enhanced the proliferation of human hair follicle dermal papilla cells (HHFDPCs) in a dose dependent manner. It induced the protein level of nuclear β-catenin, and the expressions of β-catenin downstream target genes, including LEF1, Cyc-D1 and c-Myc, in HHFDPCs. Heptapeptide significantly induced the phosphorylation of Akt and ERK, and the mRNA expressions of growth factors, including hepatocyte growth factor (HGF), keratinocyte growth factor (KGF) and vascular endothelial growth factor (VEGF), in HHFDPCs. In addition, heptapeptide significantly increased mRNA expression levels of differentiation-related transcription factors of human hair germinal matrix cells (HHGMCs) and differentiation markers of human hair outer root sheath cells (HHORSCs). Additionally, we investigated the effect of heptapeptide on human hair follicle stem cells (HHFSCs) differentiation and found that the heptapeptide reduced the mRNA and protein levels of stem cell markers, while it increased those levels of differentiation markers. These results have indicated that the heptapeptide promotes proliferation or differentiation of various types of hair follicle constituent cells through the induction of Wnt/β-catenin signaling. From the results, we have suggested that the heptapeptide in this study could be applied as a new functional material for the improvement of hair growth and alopecia.

Human adipose-derived mesenchymal stem cell spheroids improve recovery in a mouse model of elastase-induced emphysema

  • Cho, Ryeon Jin;Kim, You-Sun;Kim, Ji-Young;Oh, Yeon-Mok
    • BMB Reports
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    • v.50 no.2
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    • pp.79-84
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    • 2017
  • Emphysema, a pathologic component of the chronic obstructive pulmonary disease, causes irreversible destruction of lung. Many researchers have reported that mesenchymal stem cells can regenerate lung tissue after emphysema. We evaluated if spheroid human adipose-derived mesenchymal stem cells (ASCs) showed greater regenerative effects than dissociated ASCs in mice with elastase-induced emphysema. ASCs were administered via an intrapleural route. Mice injected with spheroid ASCs showed improved regeneration of lung tissues, increased expression of growth factors such as fibroblast growth factor-2 (FGF2) and hepatocyte growth factor (HGF), and a reduction in proteases with an induction of protease inhibitors when compared with mice injected with dissociated ASCs. Our findings indicate that spheroid ASCs show better regeneration of lung tissues than dissociated ACSs in mice with elastase-induced emphysema.

Hair Growth Effect of TS-SCLF from Schisandra chinensis Extract Fermented with Lactobacillus plantarum

  • Young Min, Woo;Jae Yong, Seo;Soo-ya, Kim;Ji Hyun, Cha;Hyun Dae, Cho;Young Kwon, Cha;Ju Tae, Jeong;Sung Min, Park;Hwa Sun, Ryu;Jae Mun, Kim;Moon Hoy, Kim;Hee-Taek, Kim;Yong-Min, Kim;Kwang Sik, Joo;Sun Mi, Lee;JungNo, Lee;Andre, Kim
    • Microbiology and Biotechnology Letters
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    • v.50 no.4
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    • pp.533-547
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    • 2022
  • This study investigated the hair growth effect of Schisandra chinensis extract (TS-SC) and TS-SC fermented by Lactobacillus plantarum (TS-SCLF) on human dermal papilla cells (hDPCs). The production of vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF-1), keratinocyte growth factor/fibroblast growth factor 7 (KGF/FGF-7) and hepatocyte growth factor (HGF), transforming growth factor beta 1 (TGF-β1) were examined. The secretion rates of VEGF and KGF/FGF-7 were high in TS-SC, and the secretion rates of IGF-1 and HGF were high in TS-SCLF. TGF-β1 was inhibited in a concentration-dependent manner in all samples. Gene expression of VEGF, IGF-1, KGF, HGF and alkaline phosphatase, relevant to hair growth, were examined. The data revealed that TS-SC and TS-SCLF successfully promoted hair growth in hDPCs. The IGF-1 gene was expressed in a dose-dependent manner in TS-SCLF. These results indicate that TS-SC and TS-SCLF fermented extract effectively promoted hair growth and gene expression relevant to hair growth in hDPCs. Used in clinical trials the test substance 'CMK-LPF01' showed a statistically significant increase in the number of hairs at 8 weeks, 16 weeks, and 24 weeks compared to before product use, and a change in hair growth, a secondary efficacy evaluation variable. Through additional research in the future, it is expected that "CMK-LPF01" can be developed as a functional material that can help alleviate symptoms of hair loss.

Proteolytic cleavages of MET: the divide-and-conquer strategy of a receptor tyrosine kinase

  • Fernandes, Marie;Duplaquet, Leslie;Tulasne, David
    • BMB Reports
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    • v.52 no.4
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    • pp.239-249
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    • 2019
  • Membrane-anchored full-length MET stimulated by its ligand HGF/SF induces various biological responses, including survival, growth, and invasion. This panel of responses, referred to invasive growth, is required for embryogenesis and tissue regeneration in adults. On the contrary, MET deregulation is associated with tumorigenesis in many kinds of cancer. In addition to its well-documented ligand-stimulated downstream signaling, the receptor can be cleaved by proteases such as secretases, caspases, and calpains. These cleavages are involved either in MET receptor inactivation or, more interestingly, in generating active fragments that can modify cell fate. For instance, MET fragments can promote cell death or invasion. Given a large number of proteases capable of cleaving MET, this receptor appears as a prototype of proteolytic-cleavage-regulated receptor tyrosine kinase. In this review, we describe and discuss the mechanisms and consequences, both physiological and pathological, of MET proteolytic cleavages.

Synovial Fluid Enhances Proliferation and Migration in Canine Keratocytes

  • Lee, Seungji;Jeong, Seong Mok;Bae, Seul-gi;Kwon, Young-sam;Yun, Sungho
    • Journal of Veterinary Clinics
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    • v.37 no.4
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    • pp.198-203
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    • 2020
  • Synovial fluid (SF) contains various factors which may be helpful for corneal stromal healing, such as cytokines, growth factors, hyaluronic acid, and proteins. Therefore, the purpose of this study was to determine the effect of SF on proliferation and migration in canine keratocytes. In order to evaluate the degree of proliferation and migration, canine keratocytes were cultured in DMEM containing 1%, 3%, 5%, or 10% SF. Real-time PCR was performed in a control group and the group treated with 5% SF, in order to measure the expression levels of factors associated with corneal wound healing. These factors included interleukin-1α (IL-1α), hepatocyte growth factor (HGF), transforming growth factor-β (TGF-β), and α-smooth muscle actin (SMA-α). Proliferation assays demonstrated that proliferation was significantly enhanced in groups treated with greater than 3% SF, as compared with that of the control group. In addition, migration in all SF-treated groups was significantly increased as compared with migration in the control group, as measured by migration assays. mRNA expression of IL-1α and HGF was significantly increased and mRNA expression of TGF-β and SMA-α was significantly decreased in the cells treated with 5% SF. These findings suggest that SF may promote corneal wound healing.