• Title/Summary/Keyword: Growth signaling

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Effects of Crataegi Fructus Hot-Water Extract on Hair Growth and Growth Factor Gene Expression of Human Dermal Papilla Cells (산사 열수추출물의 모발 성장과 모유두세포의 성장인자 유전자 발현에 대한 영향)

  • Kim, Hyeong-Key;Kim, Cheol-Hong;Yoon, Hyun-Min;Kang, Kyung-Hwa;Song, Choon-Ho
    • Korean Journal of Acupuncture
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    • v.34 no.3
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    • pp.146-155
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    • 2017
  • Objectives : This study was carried out to investigate the effects of Crataegi Fructus water extract(CFWE) on hair growth in an alopecia model of C57BL/6N mice and human dermal papilla cells(hDPCs). Methods : Six-week old mice were depilated and separated in 3 groups ; CON, MXD(2% Minoxidil), and CFWE. The treatments were applied twice a day for 18 days. The hair growth was determined photographically. The hair density, thickness and length were identified by Folliscope and the weights of body were measured. In dorsal skin tissue, the expression of hair growth-related protein was analyzed by Western blot. In hDPCs with/without $IFN-{\gamma}$, cell proliferation and the expression of hair growth-related genes were analyzed. Results : We observed that CFWE promoted hair growth compared to CON. CFWE improved the hair density, thickness and length compared to CON. CFWE increased the $Wnt/{\beta}$-catenin signaling in dorsal skin. In hDPCs, CFWE accelerated the cell proliferation and inhibited $IFN-{\gamma}$-induced hDPCs degeneration. CFWE increased the mRNA expression of ${\beta}$-catenin, Axin-2, BMP-4, FGF-7, FGF-10, and ALP compared to CON and $IFN-{\gamma}$ treated cells. Conclusions : These results suggest that CFWE has a hair regrowth activity via $Wnt/{\beta}$-catenin signaling and can be useful for the treatment of alopecia.

3-Deoxysappanchalcone Promotes Proliferation of Human Hair Follicle Dermal Papilla Cells and Hair Growth in C57BL/6 Mice by Modulating WNT/β-Catenin and STAT Signaling

  • Kim, Young Eun;Choi, Hyung Chul;Lee, In-Chul;Yuk, Dong Yeon;Lee, Hyosung;Choi, Bu Young
    • Biomolecules & Therapeutics
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    • v.24 no.6
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    • pp.572-580
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    • 2016
  • 3-Deoxysappanchalcone (3-DSC) has been reported to possess anti-allergic, antiviral, anti-inflammatory and antioxidant activities. In the present study, we investigated the effects of 3-DSC on the proliferation of human hair follicle dermal papilla cells (HDPCs) and mouse hair growth in vivo. A real-time cell analyzer system, luciferase assay, Western blot and real-time polymerase chain reaction (PCR) were employed to measure the biochemical changes occurring in HDPCs in response to 3-DSC treatment. The effect of 3-DSC on hair growth in C57BL/6 mice was also examined. 3-DSC promoted the proliferation of HDPCs, similar to Tofacitinib, an inhibitor of janus-activated kinase (JAK). 3-DSC promoted phosphorylation of ${\beta}$-catenin and transcriptional activation of the T-cell factor. In addition, 3-DSC potentiated interleukin-6 (IL-6)-induced phosphorylation and subsequent transactivation of signal transducer and activator of transcription-3 (STAT3), thereby increasing the expression of cyclin-dependent kinase-4 (Cdk4), fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF). On the contrary, 3-DSC attenuated STAT6 mRNA expression and IL4-induced STAT6 phosphorylation in HDPCs. Finally, we observed that topical application of 3-DSC promoted the anagen phase of hair growth in C57BL/6 mice. 3-DSC stimulates hair growth possibly by inducing proliferation of follicular dermal papilla cells via modulation of $WNT/{\beta}$-catenin and STAT signaling.

A Two-Strain Mixture of Rhizobacteria Elicits Induction of Systemic Resistance Against Pseudomonas syringae and Cucumber Mosaic Virus Coupled to Promotion of Plant Growth on Arabidopsis thaliana

  • Ryu Choong-Min;Murphy John F.;Reddy M.S.;Kloepper Joseph W.
    • Journal of Microbiology and Biotechnology
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    • v.17 no.2
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    • pp.280-286
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    • 2007
  • We evaluated a commercial biopreparation of plant growth-promoting rhizobacteria (PGPR) strains Bacillus subtilis GB03 and B. amyloliquefaciens IN937a formulated with the carrier chitosan (Bio Yield) for its capacity to elicit growth promotion and induced systemic resistance against infection by Cucumber Mosaic Virus (CMV) and Pseudomonas syringae pv. tomato DC3000 in Arabidopsis thaliana. The biopreparation promoted plant growth of Arabidopsis hormonal mutants, which included auxin, gibberellic acid, ethylene, jasmonate, salicylic acid, and brassinosteroid insensitive lines as well as each wild-type. The biopreparation protected plants against CMV based on disease severity in wild-type plants. However, virus titre was not lower in control plants and those treated with biopreparation, suggesting that the biopreparation induced tolerance rather than resistance against CMV. Interestingly, the biopreparation induced resistance against CMV in NahG plants, as evidenced by both reduced disease severity and virus titer. The biopreparation also elicited induced resistance against P. syringae pv. tomato in the wild-type but not in NahG transgenic plants, which degrade endogenous salicylic acid, indicating the involvement of salicylic acid signaling. Our results indicate that some PGPR strains can elicit plant growth promotion by mechanisms that are different from known hormonal signaling pathways. In addition, the mechanism for elicitation of induced resistance by PGPR may be pathogen-dependent. Collectively, the two-Bacilli strain mixture can be utilized as a biological inoculant for both protection of plant against bacterial and viral pathogens and enhancement of plant growth.

Fluvastatin inhibits advanced glycation end products-induced proliferation, migration, and extracellular matrix accumulation in vascular smooth muscle cells by targeting connective tissue growth factor

  • Hwang, Ae-Rang;Nam, Ju-Ock;Kang, Young Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.193-201
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    • 2018
  • Connective tissue growth factor (CTGF) is a novel fibrotic mediator, which is considered to mediate fibrosis through extracellular matrix (ECM) synthesis in diabetic cardiovascular complications. Statins have significant immunomodulatory effects and reduce vascular injury. We therefore examined whether fluvastatin has anti-fibrotic effects in vascular smooth muscle cells (VSMCs) and elucidated its putative transduction signals. We show that advanced glycation end products (AGEs) stimulated CTGF mRNA and protein expression in a time-dependent manner. AGE-induced CTGF expression was mediated via ERK1/2, JNK, and Egr-1 pathways, but not p38; consequently, cell proliferation and migration and ECM accumulation were regulated by CTGF signaling pathway. AGE-stimulated VSMC proliferation, migration, and ECM accumulation were blocked by fluvastatin. However, the inhibitory effect of fluvastatin was restored by administration of CTGF recombinant protein. AGE-induced VSMC proliferation was dependent on cell cycle arrest, thereby increasing G1/G0 phase. Fluvastatin repressed cell cycle regulatory genes cyclin D1 and Cdk4 and augmented cyclin-dependent kinase inhibitors p27 and p21 in AGE-induced VSMCs. Taken together, fluvastatin suppressed AGE-induced VSMC proliferation, migration, and ECM accumulation by targeting CTGF signaling mechanism. These findings might be evidence for CTGF as a potential therapeutic target in diabetic vasculature complication.

Translocation of Annexin I to the Nucleus by Epidermal Growth Factor in A549 Cells

  • Rhee, Hae-Jin;Kim, Seung-Wook;Soo-Ok, Lee;Park, Young-Min;Na, Doe-Sun
    • BMB Reports
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    • v.32 no.1
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    • pp.28-32
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    • 1999
  • Annexin I (also called lipocortin 1), a 37-kDa member of the annexin family of proteins, has been implicated in the mitogenic signal transduction by epidermal growth factor (EGF). Annexin I is phosphorylated by the EGF signal, however, the role of annexin I in the EGF signal transduction is still unknown. To transduce extracellular signals into the intracellular targets, selective translocation of the signaling molecules to their targets would be necessary. In this study, we examined the subcellular locations of annexin I during EGF signal transduction. Treatment of A549 cells with EGF resulted in the translocation of cytoplasmic annexin I to the nucleus and perinuclear region as determined by Western blot and immunofluorescent staining. The nuclear translocation of annexin I was inhibited by tyrphostin AG 1478 and genistein, the inhibitors of EGF receptor kinase and downstream tyrosine kineses, respectively. Pretreatment of cells with cyclohexamide did not inhibit the nuclear translocation. The results suggest that nuclear translocation of annexin I is controlled by a series of kinase dependent events in the EGF receptor signaling pathway and may be important in tranducing the signals by EGF.

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Molecular mechanisms of luteolin-7-O-glucoside-induced growth inhibition on human liver cancer cells: G2/M cell cycle arrest and caspase-independent apoptotic signaling pathways

  • Hwang, Yu-Jin;Lee, Eun-Ju;Kim, Haeng-Ran;Hwang, Kyung-A
    • BMB Reports
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    • v.46 no.12
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    • pp.611-616
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    • 2013
  • Luteolin-7-O-glucoside (LUT7G), a flavone subclass of flavonoids, has been found to increase anti-oxidant and anti-inflammatory activity, as well as cytotoxic effects. However, the mechanism of how LUT7G induces apoptosis and regulates cell cycles remains poorly understood. In this study, we examined the effects of LUT7G on the growth inhibition of tumors, cell cycle arrest, induction of ROS generation, and the involved signaling pathway in human hepatocarcinoma HepG2 cells. The proliferation of HepG2 cells was decreased by LUT7G in a dose-dependent manner. The growth inhibition was due primarily to the G2/M phase arrest and ROS generation. Moreover, the phosphorylation of JNK was increased by LUT7G. These results suggest that the anti-proliferative effect of LUT7G on HepG2 is associated with G2/M phase cell cycle arrest by JNK activation.

Identification of the Calcium Binding Sites in Translationally Controlled Tumor Protein

  • Kim, Moon-Hee;Jung, Yoon-Wha;Lee, Kyung-Lim;Kim, Choon-Mi
    • Archives of Pharmacal Research
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    • v.23 no.6
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    • pp.633-636
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    • 2000
  • Translationally controlled tumor protein (TCTP), also known as IgE-dependent histamine-releasing factor, is a growth-related tumor protein. Although the primary sequence of rat TCTP does not reveal any recognizable $Ca^{2+}$ -binding motif, previous studies have demonstrated that rat TCTP consisting of 172 amino acids is a $Ca^{2+}$ -binding protein. However. the region of TCTP required for $Ca^{2+}$ interaction has not been mapped to the molecule. Here, we reported that the $Ca^{2+}$ binding region of TCTP which was mapped by using a combination of deletion constructs of rat TCTP and $^{45}Ca^{2+}$-overlay assay. was confined to amino acid residues 81-112. This binding domain did not show any peculiar loop of calcium- binding motif such as CaLB domain and EF hand motif and it seems to be constituted of random coil regions neighboring the a helix. Thus, our data confirm that TCTP is a novel family of $Ca^{2+}$ -binding protein.

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Shedding; towards a new paradigm of syndecan function in cancer

  • Choi, So-Joong;Lee, Ha-Won;Choi, Jung-Ran;Oh, Eok-Soo
    • BMB Reports
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    • v.43 no.5
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    • pp.305-310
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    • 2010
  • Syndecans, cell surface heparansulfate proteoglycans, have been proposed to act as cell surface receptors and/or coreceptors to play critical roles in multiple cellular functions. However, recent reports suggest that the function of syndecans can be further extended through shedding, a cleavage of extracellular domain. Shedding constitutes an additional level for controlling the function of syndecans, providing a means to attenuate and/or regulate amplitude and duration of syndecan signals by modulating the activity of syndecans as cell surface receptors. Whether these remaining cleavage products are still capable of functioning as cell surface receptors to efficiently transduce signals inside of cells is not clear. However, shedding transforms cell surface receptor syndecans into soluble forms, which, like growth factors, may act as novel ligands to induce cellular responses by association with other cell surface receptors. It is becoming interestingly evident that shed syndecans also contribute significantly to syndecan functions in cancer biology. This review presents current knowledge about syndecan shedding and its functional significance, particularly in the context of cancer.

Molecular characterization of a novel rice(Oryza sativa L.) MAP kinase, OsEDRl, its role in defense signaling pathway.

  • Kim, Jung-A;Jwa, Nam-Soo
    • Proceedings of the Korean Society of Plant Pathology Conference
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    • 2003.10a
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    • pp.82-83
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    • 2003
  • Plants have evolved differently from animals having mobile activities. Thus, plants should have developed unique defense mechanisms against biotic/abiotic stresses to which plants are differently exposed, according to seasons. Most organisms have an conserved signaling network using mitogen-activated protein kinase (MAPK) cascade(s). The phenomenon implied that they are functionally very important in all organisms. In fact, they constitute one of the major components of signaling pathways involved in regulating a wide range of cellular activities from growth and development to cell death. Recently, complete MAPK cascade was first characterized in Arabidopsis from the receptor kinase (FLS2) through fellowing MEKKI -MKK4/MKK5-MPK3/MPK6-WRKY22/MRKY29 pathway. Whereas, MAPK cascade signaling pathway in monocot plant including rice (0ryza sativa L.), the most important of all food crops and an established monocot plant research model, MAPKinase kinase kinases (MAPKKK) of rice are the first upstream component of the MAPK cascade, but MAPKKK has been first identified and characterized in our lab and designated as, OsEDRl based on its homology with the Arabidopsis EDRI. The Arabidopsis EDRl was regarded as a negative regulator of defense response and the role of rice OsEDRl was analyzed. Transcriptional regulation of OsEDRl was detected under various stresses and immunoblotting analysis is going on to detect the level of OsEDRl protein in the mutants showing unique phenotype. We also introduced the constitutively active and the dominant negative forms of the OsEDRl for characterizing biological function.

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Genomewide Profiling of Rapamycin Sensitivity in Saccharomyces cerevisiae on Synthetic Medium

  • Chang, Yeon-Ji;Shin, Chun-Shik;Han, Dong-Hun;Kim, Ji-Yun;Kim, Kang-In;Kwon, Yong-Min;Huh, Won-Ki
    • Genomics & Informatics
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    • v.8 no.4
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    • pp.177-184
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    • 2010
  • The target of rapamycin (TOR) signaling pathway is a conserved pathway that regulates eukaryotic cell growth in response to environmental cues. Chemical genomic approaches that profile rapamycin sensitivity of yeast deletion strains have given insights into the function of TOR signaling pathway. In the present study, we analyzed the rapamycin sensitivity of yeast deletion library strains on synthetic medium. As a result, we identified 130 strains that are hypersensitive or resistant to rapamycin compared with wild-type cells. Among them, 36 genes are newly identified to be related to rapamycin sensitivity. Moreover, we found 16 strains that show alteration in rapamycin sensitivity between complex and synthetic media. We suggest that these genes may be involved in part of TOR signaling activities that is differentially regulated by media composition.