Paracrine Factor

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Janice M. Bahr - One of the best experts on this subject based on the ideXlab platform.

  • Germinal Disc-Derived Epidermal Growth Factor: A Paracrine Factor to Stimulate Proliferation of Granulosa Cells1
    2016
    Co-Authors: Humphrey H.-c. Yao, Janice M. Bahr
    Abstract:

    The germinal disc (GD) of the chicken oocyte produces fac-tors that influence proliferation and differentiation of granulosa cells. Granulosa cells proximal to the GD are more proliferative, whereas granulosa cells distal to the GD are more differentiated. Previously, we had found epidermal growth Factor (EGF) was present in the GD. In this study, we tested the hypothesis that EGF is the GD-derived Paracrine Factor that stimulates prolif-eration of granulosa cells. Northern analysis, reverse transcrip-tion-polymerase chain reaction, and radioimmunoassay indicat-ed that the GD and granulosa cells but not theca cells are the sources of EGF in chicken preovulatory follicles. However, only the conditioned medium from the GD region (GDR 5 GD 1 overlying granulosa cells) but not the granulosa cell-conditioned medium stimulated proliferation of granulosa cells. Pretreatment of conditioned media with EGF antibody abolished the prolif-eration-stimulating effect of the GDR-conditioned medium. We conclude that EGF is one of the Paracrine Factors produced by the GD to stimulate proliferation of granulosa cells. Granulosa cells proximal to the GD express a proliferative phenotype pos-sibly because they are exposed to a greater amount of EGF de-rived from the GD. follicle, granulosa cells, growth Factors, ovary, ovu

  • Germinal Disc-Derived Epidermal Growth Factor: A Paracrine Factor to Stimulate Proliferation of Granulosa Cells
    Biology of reproduction, 2001
    Co-Authors: Humphrey H.-c. Yao, Janice M. Bahr
    Abstract:

    The germinal disc (GD) of the chicken oocyte produces Factors that influence proliferation and differentiation of granulosa cells. Granulosa cells proximal to the GD are more proliferative, whereas granulosa cells distal to the GD are more differentiated. Previously, we had found epidermal growth Factor (EGF) was present in the GD. In this study, we tested the hypothesis that EGF is the GD-derived Paracrine Factor that stimulates proliferation of granulosa cells. Northern analysis, reverse transcription-polymerase chain reaction, and radioimmunoassay indicated that the GD and granulosa cells but not theca cells are the sources of EGF in chicken preovulatory follicles. However, only the conditioned medium from the GD region (GDR = GD + overlying granulosa cells) but not the granulosa cell-conditioned medium stimulated proliferation of granulosa cells. Pretreatment of conditioned media with EGF antibody abolished the proliferation-stimulating effect of the GDR-conditioned medium. We conclude that EGF is one of the Paracrine Factors produced by the GD to stimulate proliferation of granulosa cells. Granulosa cells proximal to the GD express a proliferative phenotype possibly because they are exposed to a greater amount of EGF derived from the GD.

Meijing Wang - One of the best experts on this subject based on the ideXlab platform.

  • sca 1 cardiac stem cells mediate acute cardioprotection via Paracrine Factor sdf 1 following myocardial ischemia reperfusion
    PLOS ONE, 2011
    Co-Authors: Chunyan Huang, Mariuxi C Manukyan, Jeffrey A Poynter, Meijing Wang
    Abstract:

    Background: Cardiac stem cells (CSCs) promote myocardial recovery following ischemia through their regenerative properties. However, little is known regarding the implication of Paracrine action by CSCs in the setting of myocardial ischemia/reperfusion (I/R) injury although it is well documented that non-cardiac stem cells mediate cardioprotection via the production of Paracrine protective Factors. Here, we studied whether CSCs could initiate acute protection following global myocardial I/R via Paracrine effect and what component from CSCs is critical to this protection. Methodology/Principal Findings: A murine model of global myocardial I/R was utilized to investigate Paracrine effect of Sca-1+ CSCs on cardiac function. Intracoronary delivery of CSCs or CSC conditioned medium (CSC CM) prior to ischemia significantly improved myocardial function following I/R. siRNA targeting of VEGF in CSCs did not affect CSC-preserved myocardial function in response to I/R injury. However, differentiation of CSCs to cardiomyocytes (DCSCs) abolished this protection. Through direct comparison of the protein expression profiles of CSCs and DCSCs, SDF-1 was identified as one of the dominant Paracrine Factors secreted by CSCs. Blockade of the SDF-1 receptor by AMD3100 or downregulated SDF-1 expression in CSCs by specific SDF-1 siRNA dramatically impaired CSC-induced improvement in cardiac function and increased myocardial damage following I/R. Of note, CSC treatment increased myocardial STAT3 activation after I/R, whereas downregulation of SDF-1 action by blockade of the SDF-1 receptor or SDF-1 siRNA transfection abolished CSC-induced STAT3 activation. In addition, inhibition of STAT3 activation attenuated CSC-mediated cardioprotection following I/R. Finally, post-ischemic infusion of CSC CM was shown to significantly protect I/R-caused myocardial dysfunction. Conclusions/Significance: This study suggests that CSCs acutely improve post-ischemic myocardial function through Paracrine Factor SDF-1 and up-regulated myocardial STAT3 activation.

  • vegf is critical for stem cell mediated cardioprotection and a crucial Paracrine Factor for defining the age threshold in adult and neonatal stem cell function
    American Journal of Physiology-heart and Circulatory Physiology, 2008
    Co-Authors: Troy A Markel, Meijing Wang, Yue Wang, Jeremy L Herrmann, Paul R Crisostomo, Nathan M Novotny, Christine M Herring, Jiangning Tan, Tim Lahm, Daniel R Meldrum
    Abstract:

    Bone marrow mesenchymal stem cells (MSCs) may be a novel treatment modality for organ ischemia, possibly through the release of beneficial Paracrine Factors. However, an age threshold likely exists...

  • vegf is critical for stem cell mediated cardioprotection and a crucial Paracrine Factor for defining the age threshold in adult and neonatal stem cell function
    American Journal of Physiology-heart and Circulatory Physiology, 2008
    Co-Authors: Troy A Markel, Meijing Wang, Yue Wang, Jeremy L Herrmann, Paul R Crisostomo, Nathan M Novotny, Christine M Herring, Jiangning Tan, Tim Lahm, Daniel R Meldrum
    Abstract:

    Bone marrow mesenchymal stem cells (MSCs) may be a novel treatment modality for organ ischemia, possibly through the release of beneficial Paracrine Factors. However, an age threshold likely exists as to when MSCs gain their beneficial protective properties. We hypothesized that 1) VEGF would be a crucial stem cell Paracrine mediator in providing postischemic myocardial protection and 2) small-interfering (si)RNA ablation of VEGF in adult MSCs (aMSCs) would equalize the differences observed between aMSC- and neonatal stem cell (nMSC)-mediated cardioprotection. Female adult Sprague-Dawley rat hearts were subjected to ischemia-reperfusion injury via Langendorff-isolated heart preparation (15 min equilibration, 25 min ischemia, and 60 min reperfusion). MSCs were harvested from adult and 2.5-wk-old neonatal mice and cultured under normal conditions. VEGF was knocked down in both cell lines by VEGF siRNA. Immediately before ischemia, one million aMSCs or nMSCs with or without VEGF knockdown were infused into the coronary circulation. The cardiac functional parameters were recorded. VEGF in cell supernatants was measured via ELISA. aMSCs produced significantly more VEGF than nMSCs and were noted to increase postischemic myocardial recovery compared with nMSCs. The knockdown of VEGF significantly decreased VEGF production in both cell lines, and the pretreatment of these cells impaired stem cell-mediated myocardial function. The knockdown of VEGF in adult stem cells equalized the myocardial functional differences observed between adult and neonatal stem cells. Therefore, VEGF is a critical Paracrine mediator in facilitating postischemic myocardial recovery and likely plays a role in mediating the observed age threshold during stem cell therapy.

Vincent J Hearing - One of the best experts on this subject based on the ideXlab platform.

  • characterization of the bioactive motif of neuregulin 1 a fibroblast derived Paracrine Factor that regulates the constitutive color and the function of melanocytes in human skin
    Pigment Cell & Melanoma Research, 2012
    Co-Authors: Wonseon Choi, Ludger Kolbe, Vincent J Hearing
    Abstract:

    Summary Interactions between melanocytes and neighboring cells in the skin (keratinocytes and fibroblasts) play important roles in regulating human skin color. We recently reported that neuregulin-1 (NRG1) is highly expressed in fibroblasts from Fitzpatrick type VI skin (the darkest) and at least in part determines the constitutive color of human skin. We have now characterized the bioactive motif of NRG1 that is involved in modulating melanin production in human melanocytes. We found that 8-mer motifs (PSRYLCKC and LCKCPNEF) increased melanin production but did not increase the proliferation of melanocytes; the minimum fragment that could elicit that effect was the tetrapeptide LCKC. This smaller bioactive peptide might have an advantage in clinical applications in which it modulates only pigmentation and does not stimulate melanocyte proliferation.

  • the fibroblast derived Paracrine Factor neuregulin 1 has a novel role in regulating the constitutive color and melanocyte function in human skin
    Journal of Cell Science, 2010
    Co-Authors: Wonseon Choi, Rainer Wolber, Wolfram Gerwat, Tobias Mann, Jan Batzer, Christoph Smuda, Hongfang Liu, Ludger Kolbe, Vincent J Hearing
    Abstract:

    Interactions between melanocytes and neighboring cells in the skin are important in regulating skin color in humans. We recently demonstrated that the less pigmented and thicker skin on the palms and soles is regulated by underlying fibroblasts in those areas, specifically via a secreted Factor (DKK1) that modulates Wnt signaling. In this study, we tested the hypothesis that dermal fibroblasts regulate the constitutive skin color of individuals ranging from very light to very dark. We used microarray analysis to compare gene expression patterns in fibroblasts derived from lighter skin types compared to darker skin types, with a focus on secreted proteins. We identified a number of genes that differ dramatically in expression and, among the expressed proteins, neuregulin-1, which is secreted by fibroblasts derived from dark skin, effectively increases the pigmentation of melanocytes in tissue culture and in an artificial skin model and regulates their growth, suggesting that it is one of the major Factors determining human skin color.

Seiji Arase - One of the best experts on this subject based on the ideXlab platform.

  • the chemotactic effect of a dermal papilla cell derived Factor on outer root sheath cells
    Journal of Dermatological Science, 2001
    Co-Authors: Takeshi Fujie, Yoshio Urano, Shoji Katoh, Hajimu Oura, Seiji Arase
    Abstract:

    Abstract The effect of cultured normal human dermal papilla cells (DPCs) and conditioned medium prepared with cultured DPCs on chemotactic migration of human hair outer root sheath cells (ORSCs) was examined quantitatively. ORSCs showed significantly increased migration toward both cultured DPCs and the conditioned medium suggesting that DPCs produce and secrete a Paracrine Factor(s), which attracts hair follicle epithelial cells. Some soluble Factors, which are reportedly produced by DPCs, such as insulin-like growth Factor-I (IGF-I), hepatocyte growth Factor (HGF), vascular endothelial cell growth Factor (VEGF), and transforming growth Factor-β1 (TGF-β1), were also examined. ORSCs showed dramatically increased migration toward IGF-I and HGF at concentrations of 1–10 ng/ml. On the other hand, neither VEGF nor TGF-β1 showed any effect on the chemotaxis of ORSCs. It is interesting that all Factors involving mitogenic activity did not always have chemotactic activity for ORSCs. This is the first report to establish that IGF-I and HGF have not only a growth stimulatory but also a chemotactic effect on ORSCs. In addition, the method presented here may help to simplify chemotaxis assays of any type of epithelial keratinocytes with poor mobility.

  • the chemotactic effect of a dermal papilla cell derived Factor on outer root sheath cells
    Journal of Dermatological Science, 2001
    Co-Authors: Takeshi Fujie, Yoshio Urano, Shoji Katoh, Hajimu Oura, Seiji Arase
    Abstract:

    The effect of cultured normal human dermal papilla cells (DPCs) and conditioned medium prepared with cultured DPCs on chemotactic migration of human hair outer root sheath cells (ORSCs) was examined quantitatively. ORSCs showed significantly increased migration toward both cultured DPCs and the conditioned medium suggesting that DPCs produce and secrete a Paracrine Factor(s), which attracts hair follicle epithelial cells. Some soluble Factors, which are reportedly produced by DPCs, such as insulin-like growth Factor-I (IGF-I), hepatocyte growth Factor (HGF), vascular endothelial cell growth Factor (VEGF), and transforming growth Factor-beta1 (TGF-beta1), were also examined. ORSCs showed dramatically increased migration toward IGF-I and HGF at concentrations of 1-10 ng/ml. On the other hand, neither VEGF nor TGF-beta1 showed any effect on the chemotaxis of ORSCs. It is interesting that all Factors involving mitogenic activity did not always have chemotactic activity for ORSCs. This is the first report to establish that IGF-I and HGF have not only a growth stimulatory but also a chemotactic effect on ORSCs. In addition, the method presented here may help to simplify chemotaxis assays of any type of epithelial keratinocytes with poor mobility.

Dominique P.v. De Kleijn - One of the best experts on this subject based on the ideXlab platform.

  • mesenchymal stem cell derived exosomes increase atp levels decrease oxidative stress and activate pi3k akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia reperfusion injury
    Stem Cell Research, 2013
    Co-Authors: Fatih Arslan, Mirjam B Smeets, Lars Akeroyd, Eissa N E Aguor, Leo Timmers, Gerard Pasterkamp, Harold V.m. Van Rijen, Andre Choo, Pieter A Doevendans, Dominique P.v. De Kleijn
    Abstract:

    Abstract We have previously identified exosomes as the Paracrine Factor secreted by mesenchymal stem cells. Recently, we found that the key features of reperfusion injury, namely loss of ATP/NADH, increased oxidative stress and cell death were underpinned by proteomic deficiencies in ischemic/reperfused myocardium, and could be ameliorated by proteins in exosomes. To test this hypothesis in vivo, mice (C57Bl6/J) underwent 30 min ischemia, followed by reperfusion (I/R injury). Purified exosomes or saline was administered 5 min before reperfusion. Exosomes reduced infarct size by 45% compared to saline treatment. Langendorff experiments revealed that intact but not lysed exosomes enhanced viability of the ischemic/reperfused myocardium. Exosome treated animals exhibited significant preservation of left ventricular geometry and contractile performance during 28 days follow-up. Within an hour after reperfusion, exosome treatment increased levels of ATP and NADH, decreased oxidative stress, increased phosphorylated-Akt and phosphorylated-GSK-3β, and reduced phosphorylated-c-JNK in ischemic/reperfused hearts. Subsequently, both local and systemic inflammation were significantly reduced 24 h after reperfusion. In conclusion, our study shows that intact exosomes restore bioenergetics, reduce oxidative stress and activate pro-survival signaling, thereby enhancing cardiac function and geometry after myocardial I/R injury. Hence, mesenchymal stem cell-derived exosomes are a potential adjuvant to reperfusion therapy for myocardial infarction.

  • reduction of myocardial infarct size by human mesenchymal stem cell conditioned medium
    Stem Cell Research, 2008
    Co-Authors: Leo Timmers, Reida Menshawe El Oakley, Fatih Arslan, Gerard Pasterkamp, Andre Choo, Imo E. Hoefer, Jeffrey S Armstrong, Jan J Piek, Pieter A Doevendans, Dominique P.v. De Kleijn
    Abstract:

    Abstract Although Paracrine effects of mesenchymal stem cells (MSCs) have been suggested previously, cardioprotection by human MSC secretions has never been demonstrated. Human MSC-conditioned medium (CM) was collected by following a clinically compliant protocol. In a porcine model of ischemia and reperfusion injury, intravenous and intracoronary MSC-CM treatment significantly reduced myocardial nuclear oxidative stress as determined by immunostaining for 8-hydroxy-2′-deoxyguanosine. In addition, expression levels of phospho-SMAD2 and active caspase 3 were diminished following CM treatment, suggesting that TGF-β signaling and apoptosis were reduced. This was associated with a 60% reduction in infarct size and marked improvement of systolic and diastolic cardiac performance as assessed with echocardiography and pressure volume loops. Fractionation studies revealed that only the fraction of the CM containing products > 1000 kDa (100–220 nm) provided cardioprotection in a mouse model of ischemia and reperfusion injury. This indicates that the responsible Paracrine Factor of human MSCs is likely a large complex rather than a single small molecule. These data identify human MSC-CM as a promising therapeutic option to reduce myocardial infarct size in patients with acute MI and suggest that the use of stem cell secretions could extend the applicability of stem cells for therapeutic purposes.