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MOLECULAR CONTROLS OF EPIDERMAL GROWTH AND DIFFERENTIATION: TRANSFORMING GROWTH FACTORE
Son, Youngsook,Fuchs, Elaine Korean Society of ToxicologyKorea Environmental Mu 1991 Toxicological Research Vol.7 No.2
In the epidermis of skin, a fine balance exists between proliferating progenitor cells and terminally differentiating cells. We examined the effects of TGF-betas and retinoic acid (RA) on controlling this balance in normal human epidermal keratinocytes cultured under conditions where most morphological and biochemical features of epidermis in vivo are retained. Our results revealed marked and pleiotropic effects of both TGF-beta and RA on kerationcytes. In contrast to retinoids, TGF-betas acted on mitotically active basal cells to retard cell proliferation.
Perspectives on Mesenchymal Stem Cells: Tissue Repair, Immune Modulation, and Tumor Homing
홍현숙,Youngsook Son,김영훈 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.2
Mesenchymal stem cells (MSCs) or MSC-like cells have been identified in a variety of different tissues that share molecular expression profiles and biological functions but also retain a unique differentiation preference depending on their tissue origins. MSCs play beneficial roles in the healing of damaged tissue by directly differentiating to many different resident cell types and/or by secreting several trophic factors that aid tissue repair. Aside from MSCs’ reparative stem cell function, they drive immune responses toward immunosuppression and anti-inflammation. This novel function of MSCs opens up new avenues for clinical development of MSC immune-therapeutics to treat uncontrollable, life threatening, severe, chronic inflammation and autoimmune disease. Unexpectedly high rates of MSCs’ tumor homing capacity and their tumor supporting capability have also been noted in tumor-bearing animal models. In this review, we will discuss MSCs’ basic cell biology and perspectives on MSCs in terms of tissue repair, immune modulation, and tumor homing.
Park, Ki-Sook,Lee, Eun-Gyu,Son, Youngsook John Wiley Sons 2014 Journal of biomedical materials research. Part A Vol.102 No.7
<P>Human dermal fibroblasts were inoculated into chitosan sponge scaffolds coated with type I collagen and it might be developed as a dermal substitute and/or dressing material. The application of 14% uniaxial cyclic strain to the cellular scaffolds affected the characteristics of the seeded human dermal fibroblasts. Cyclic strain enhanced cellular proliferation, the activity of metalloproteinase-2, and the expression of extracellular matrix proteins such as fibronectin. Moreover, cyclic strain increased the expression of vascular endothelial growth factor (VEGF) and interleukin (IL)-6, which are critical to wound healing. Even under static culture (strain, 0%) following 14% cyclic strain, the expression of VEGF and IL-6, which had increased under 14% strain, was amplified or maintained for at least 3 days. Uniaxial cyclic strain may enhance the wound-healing potential of human dermal fibroblasts seeded on chitosan scaffolds through the changes in the cellular characteristics of the fibroblasts when the cellular scaffold is transplanted into skin wounds, especially chronic wounds such as diabetic wounds.</P>
Choi, Hyeongwon,Shin, Min Kyung,Ahn, Hey Jin,Lee, Tae Ryong,Son, Youngsook,Kim, Kyung Sook John Wiley Sons, Inc. 2018 Microscopy research and technique Vol.81 No.11
<P><B>Abstract</B></P><P>Chemical agents that can potentially cause skin irritation are typically tested in animal models or in vitro assays of cell viability or cytokine expression. However, these methods do not always provide translatable results and are not sufficiently sensitive for subtoxicity detection. Here, we introduce the mechanical properties of keratinocytes as novel endpoints for the safety assessment of chemical agents at the subtoxicity level. Human primary keratinocytes were treated with various concentrations of sodium lauryl sulfate (SLS) and their biological properties (proliferation, membrane integrity, inflammatory response, and morphology) were observed. Their biomechanical and geometrical parameters (stiffness and surface roughness) were also investigated by atomic force microscopy. Keratinocyte morphophysiological changes and inflammatory responses were significant at ≥25 μM SLS. The keratinocytes became less stiff due to changes in the distribution of F‐actin filaments and α‐tubulin; these changes were significant even at lower doses of SLS (≤10 μM). The morphophysiological changes of keratinocytes were clearly seen at a relatively high dose of SLS, while the mechanical properties of keratinocytes responded linearly to SLS at lower doses. Therefore, changes in mechanical properties can be used as new endpoints for in vitro toxicity testing with keratinocytes.</P>
Zhang, Mingzi,Ahn, Woosung,Kim, Sumin,Hong, Hyun Sook,Quan, Chengshi,Son, Youngsook John Wiley & Sons Ltd. 2017 Microcirculation Vol.24 No.8
<P><B>Abstract</B></P><P><B>Objective</B></P><P>The aim of this study was to evaluate the angiogenicity of a combination of BM‐EPCs and BM‐MSCs in vitro in the presence of SP and its working mechanism.</P><P><B>Methods</B></P><P>BM‐MSCs and BM‐EPCs were cocultured with or without SP. ELISA and RT‐PCR were performed to detect angiogenic factors such as VEGF and PDGF‐BB. N‐cadherin was detected by Western blot analysis. The tubular network‐forming ability was evaluated by a Matrigel tube‐forming assay.</P><P><B>Results</B></P><P>BM‐EPCs coculture with BM‐MSCs strongly stimulated the recruitment of BM‐MSCs onto the BM‐EPC‐generated endothelial tubular network. Upon SP treatment, endothelial branching point, tubule length, and tubular recruitment of BM‐MSCs were further increased and stabilized. The coculture of BM‐EPCs and BM‐MSCs synergistically stimulated expression of VEGF, VEGF receptor, N‐cadherin, and PDGF‐BB, all of which were further enhanced by SP treatment. Blockade of PDGF‐BB by its functional blocking antibodies markedly reduced the BM‐MSC incorporation into the endothelial tubules. SP‐pretreated BM‐MSCs were preferentially incorporated into the preformed BM‐EPC tubular network.</P><P><B>Conclusions</B></P><P>BM‐EPCs along with SP promote the pericyte‐like coverage of BM‐MSCs on endothelial tubules possibly through the induction of PDGF‐BB.</P>
위암세포주에서 Recombinant Human Interferon-r와 Adriamycin의 투여순서가 항암효과에 미치는 영향
홍원선,손영숙,김창민,강윤구,이춘택,김유철,임영혁,남현석,이진오,강태웅 大韓免疫學會 1993 大韓免疫學會誌 Vol.15 No.-
Numerous previous studies, both in vitro and in vivo, have demonstrated that the cytotoxicity can be enhanced by the combination of chemotherapeutic agent and interferons(IFNs) in various types of cancer cells. We have previously reported that combined treatment of MKN-45, human gastric adenocarcinoma cells, with adriamycin(ADM) and recombinant human interferon-r(rh-IFN-r) increased in the cytotoxicity. In this study, the effects of combination timing of rh-IFN-r and ADM on the cytotoxicity against MKN-45 were investigated using MTT assay. MKN-45 was treated with rh-IFN-r and ADM in vitro on three schedules : Treat A ; rh-IFN-r and ADM were treated simultaneously, Treat B ; rh-IFN-r was treated 24 hours after the treatment with ADM, Treat C ; rh-IFN-r was treated for 72 hours and followed by the treatment with ADM. The survival of MKN -45 was inhibited by ADM dose-dependently. 102 and 103U/ml of rh-IFN-r significantly inhibited the survival of MKN-45(% survival : 35.1 ±-1.2% and 34.4 ±1.1% in Treat A and 42.5 ± 2.1% and 45.9-±2.5% in Treat C, respectively). However no difference in the survival was observed between 102 and 103U/ml of rh-IFN-r. Combined treatment with rh-IFN-r and ADM significantly augmented the cytotoxicity at low concentrations of ADM. Combined effects of rh-IFN-r and ADM were evaluated using IC30(,ag/ml) to ADM. IC30s of MKN-45 in Treat A, B and C at 102 U/ml of rh -IFN-r _ were 0.019 -?- 0.003, 0.045 :I:0.001 and 0.054 ± 0.012, respectively, while IC30 of MKN-45 treated with ADM alone was 0.052±0.004. IC30s of MKN-45 in ADM alone group, Treat A, Treat B and Treat C at 103U/ml of rh-IFN-r were 0.047 ±0.003, 0.004 -±0.001, 0.031 ±0.004 and 0.056 0.008, respectively. These results indicate IC30s of Treat A and B were significantly lower than those of ADM alone(p<0.05) and IC30s of Treat A was significantly lower than those of Treat B(p <0.01). IC30s of Treat C, however, were not different from those of ADM alone. From these results demonstrating that cytotoxic effects were increased by the combination of rh-IFN-r and ADM in the order, Treat A > Treat B> Treat C, it can be concluded that the simultaneous administration of rh-IFN-r and ADM may be the most effective method to combine these two therapeutic modalties.