Cell signaling in human keratinocytes

손상욱 ( Sang Wook Son ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.1

1) Cell signaling - A part of any communication process that governs basic activities of cells and coordinates all cell actions. - The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity as well as normal tissue homeostasis. Errors in signaling interactions and cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes. - By understanding cell signaling, diseases may be treated more effectively and, theoretically, artificial tissues may be created. - Analysis of cell signaling networks requires a combination of experimental and theoretical approaches including the development and analysis of simulations and modeling. 2) Transcription factor (or sequence-specific DNA-binding factor) - A protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. - This helps to regulate the expression of genes near that sequence. A defining feature of transcription factors is that they contain at least one DNA-binding domain (DBD), which attaches to a specific sequence of DNA adjacent to the genes that they regulate. - Transcription factors bind to either enhancer or promoter regions of DNA adjacent to the genes that they regulate. Depending on the transcription factor, the transcription of the adjacent gene is either up- or down-regulated. Transcription factors use a variety of mechanisms for the regulation of gene expression. - 3) Luciferase - Used as a reporter to assess the transcriptional activity in cells that are transfected with a genetic construct containing the luciferase gene under the control of a promoter of interest. - Light is emitted when luciferase acts on the appropriate luciferin substrate. Photon emission can be detected by light sensitive apparatus such as a luminometer or modified optical microscopes. This allows observation of biological processes. 4) Small interfering RNA (siRNA) technology - emerged as a powerful genetic tool to investigate gene function in mammalian cells. - small pieces of double-stranded (ds) RNA, usually about 21 nucleotides long, with 3` overhangs (2 nucleotides) at each end that can be used to "interfere" with the translation of proteins by binding to and promoting the degradation of messenger RNA (mRNA) at specific sequences. - The choice of transfection reagent is critical for success in siRNA experiments. It is essential to use transfection reagents formulated to deliver small RNAs. 5) Transfection - In this technique siRNA first must be designed against the target gene. Once the siRNA is configured against the gene it has to be effectively delivered through a transfection protocol. - Delivery is usually done by cationic liposomes, polymer nanoparticles, and lipid conjugation. This method is advantageous because it can deliver siRNA to most types of cells, has high efficiency and reproducibility, and is offered commercially. - The most common commercial reagents for transfection of siRNA are Lipofectamine and Neon Transfection. 6) Chromatin Immunoprecipitation (ChIP) - A type of immunoprecipitation experimental technique used to investigate the interaction between proteins and DNA in the cell. - It aims to determine whether specific proteins are associated with specific genomic regions, such as transcription factors on promoters or other DNA binding sites, and possibly defining cistromes.

Inbong Memorial Lecture : Thymic stromal lymphopoietin downregulates filaggrin expression by STAT3 and ERK phosphorylation in keratinocytes

손상욱 ( Sang Wook Son ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.1

A number of recent studies support the fact that filaggrin is a critical barrier protein. For instance, murine models of filaggrin haploinsufficiency promote a barrier defect and percutaneous allergen sensitization. Loss-of-function mutations of the filaggrin gene (FLG) in human skin strongly predispose ichthyosis vulgaris and atopic dermatitis (AD). Although the frequency and the genetic spectrum of FLG mutations are distinct in each population, approximately 25-50% of patients with AD have been reported to carry FLG mutations. However, all the patients with AD have skin barrier defect. Furthermore, one study showed that the acute lesional skin of patients with AD with the FLG mutation exhibited lower levels of filaggrin expression compared with the nonlesional skin in the same patient. In another report, the authors noted that while there is no correlation between FLG mutations and psoriasis, decreased filaggrin expression has been detected in psoriatic skin, especially in acute plaques. The researchers focused on these observations and anticipated that there should be additional mechanisms to modulate filaggrin expression. We were more concerned with thymic stromal lymphopoietin (TSLP) and its main source, keratinocytes, because TSLP is the initiating key molecule in immunopathogenesis of AD. TSLP is an IL-7-like cytokine which activates myeloid dendritic cells to induce an inflammatory Th2 response. TSLP is highly expressed in acute and chronic AD lesions mainly by keratinocytes in human skin. There are a number of evidences to prove that TSLP is crucial in development of AD. Keratinocytes and its product, TSLP are in the middle of the pathogenesis of atopic inflammation from the very early stage. However, the effects of TSLP on human keratinocytes remain unknown. The aim of this study was to investigate whether TSLP can modulate filaggrin expression in keratinocytes. In this study, we demonstrated the presence of TSLP receptor in human keratinocytes and skin. We also found that filaggrin expression was significantly reduced by TSLP in human keratinocytes and this process was mediated by STAT3- and/or ERK1/2-dependent signaling pathways. These results suggest that TSLP and the related downstream molecules might be a target to ameliorate the disrupted barrier in patients with AD.

색소레이저 ( Flashlamp Pulsed Tunable Dye Laser ) 로 치료한 국한성 혈관각화종

손상욱 ( Sang Wook Son ),홍승현 ( Seung Hyun Hong ),이길주 ( Gil Ju Yi ),송해준 ( Hae Jun Song ),오칠환 ( Chil Hwan Oh ) 대한피부과학회 1998 대한피부과학회지 Vol.36 No.1

Angiokeratoma circumscriptum is present at birth or early childhood and is an uncommon dermatosis characterized by papules and small nodules that may coalesce to form plaques. Histopathologically, there are varying degrees of hyperkeratosis, papillomatosis, and irregular acanthosis. In the papillary dermis, greatly dilated capillaries are observed, The acanthotic epidermis encircles the vascular spaces(blood cysts) where, occasionally, organized thrombi may be found. The use of pulsed-dye lasers to treat cutaneous vascular lesions is based on the theory of selective photothermolysis. We report a case of an angiokeratoma circumscriptum in an 48-year-old woman for whom the flashlamp pulsed tunable dye laser proved to be a highly successful means of treatment. (Korean J Dermatol 1998;36(1) : 152-155)

Demonstration and education of patch testing

손상욱 ( Sang Wook Son ) 대한피부과학회 2013 대한피부과학회 학술발표대회집 Vol.65 No.2

Patch testing is a standardized biological provocation test of investigating type IV hypersensitivity reactions. Patch testing is an essential investigation to identify specific allergens or to make the diagnosis of allergic contact dermatitis (ACD). Patch testing is indicated when contact allergy is suspected. The most commonly accepted technique for patch testing involves the application of test allergens under occlusion onto the skin of the upper back for two days. The patches typically are left in place for two days. The initial evaluation is generally performed 30 minutes after the patches are removed, when the transient erythema has resolved. The time of the second reading varies, but generally is on day four. An additional reading at day seven may be useful to identify a small number of late, positive reactions, in particular to neomycin and corticosteroids. Despite the confirmatory value of patch testing, dermatologists are reluctant to use patch testing. The substantial challenge in diagnostic patch testing is that reading is subjective and morphology of the patch-test response can be a confusing guide to whether the response is allergic or irritant. Therefore, there exists considerable inter-individual variation in how patch tests are both read and then interpreted by clinicians. Interpretation of the relevance of the reactions is difficult and perhaps requiring repeated open application testing, work-site visits. The clinician`s knowledge and experience can greatly affect the results. In this program, we will discuss standardized method and interpretation of patch testing as well as common allergens in Korean patients with contact dermatitis.

Atopic dermatitis

손상욱 ( Sang Wook Son ) 대한피부과학회 2017 대한피부과학회 학술발표대회집 Vol.69 No.2

Quiz 5

손상욱 ( Sang Wook Son ) 대한피부과학회 2016 대한피부과학회 학술발표대회집 Vol.68 No.2

Education: 1989-1995 Korea University College of Medicine (MD), Seoul, Korea 1997-1995 Korea University College of Medicine (MS), Seoul, Korea 1999-2002 Korea University College of Medicine (PhD), Seoul, Korea Training and Fellowship Appointments: 1996-2000 Dermatology residency, Korea University Medical Center, Seoul, Korea 2000-2002 Dermatology fellow, Korea University Hospital, Seoul, Korea 2009-2010 Visiting Professor, Institute of Biomaterials and Biomedical Engineering, University of Toronto, Cananda Faculty Appointment: 2003-2005 Instructor, Dermatology, Korea University College of Medicine 2005-2010 Assistant professor, Dermatology, Korea University College of Medicine 2010-2015 Associate professor, Dermatology, Korea University College of Medicine 2015-present Professor, Dermatology, Korea University College of Medicine Memberships: 2016-present Medical Insurance, Korean Dermatological Association 2015-present Academic Affairs, Korean Atopic Dermatitis Association 2013-present Korean Society of Contact Dermatitis and Skin Allergy 2015-present Executive, Korean Society for Investigative Dermatology 2015-present Publication, Korean Medical Society for Cosmetics

Symposium 4-2 (SYP 4-2) : Atopic dermatitis caused by sodium metabisulfite

손상욱 ( Sang Wook Son ) 대한피부과학회 2014 대한피부과학회 학술발표대회집 Vol.66 No.2

Atopic dermatitis (AD) is a chronic inflammatory cutaneous disease that is largely described by two themes of pathologic mechanisms, inflammation and barrier dysfunction. Most patients with AD show reduced expression of filaggrin, which plays an important role to maintain intact skin barrier function. The most important function of skin is to form a barrier of the organism against the external environment. To perform this function the epidermis undergoes keratinization, a process in which keratinocytes progressively mature from basal layer to flattened squames of the stratum corneum. Filaggrin, one of key proteins in cornified envelope, binds to and aggregate keratin intermediate filaments to collapse into tight bundles, forming the flattened corneocytes. Further, filaggrin is degraded to release hygroscopic amino acids, so-called ‘natural moisturizing factors’, which contribute to water retention and maintenance of low pH. A number of recent studies support the fact that filaggrin is a critical barrier protein. For instance, murine models of filaggrin haploinsufficiency promote a barrier defect and percutaneous allergen sensitization. These FLG null mutations are involved not only in barrier disruption but also in immunopathogenesis by allowing high level of allergen sensitization. Inversely, inflammatory cytokines produced by re-attack of the sensitizing antigen also break the skin barrier. Skin barrier dysfunction and inflammation may contribute to a vicious cycle of AD. Allergic contact dermatitis caused by sulfites is frequent and often relevant. One should be aware of possible relevant sources of exposure, particularly in occupational settings such as hairdressing and the food industry, and in pharmaceutical and cosmetic products. Patch testing with sodium metabisulfite, which seems to be the best indicator for sulfite contact allergy, is also useful in cases of immediate reactions to sulfite-containing products.

Thalidomide로 치료한 피부 형질세포종

황을상 ( Eul Sang Hwang ),손상욱 ( Sang Wook Son ),김일환 ( Il Hwan Kim ) 대한피부과학회 2004 대한피부과학회지 Vol.42 No.10

Acute Diffuse and Total Alopecia of the Female Scalp

손수빈 ( Soo Bin Son ),신재빈 ( Jae Bin Shin ),서수홍 ( Soo Hong Seo ),손상욱 ( Sang Wook Son ),김일환 ( Ill Hwan Kim ) 대한피부과학회 2008 대한피부과학회지 Vol.46 No.10

Diffuse alopecia areata is the least common clinical type of alopecia, and this diffuse form lacks the characteristic hairless patches of alopecia and it begins as diffuse hair loss. Diffuse alopecia areata has been poorly characterized. In 2002, there was a suggestion to define this form of alopecia areata as acute, diffuse and total alopecia of the female scalp (ADTAFS). ADTAFS is characterized by a marked female predominance, tissue eosinophilia and a uniquely short clinical course. We report here on one case of ADTAFS. (Korean J Dermatol 2008;46(10):1407∼1410)

Mohs 미세도식 수술로 치료한 피부 악성 종양 123예의 임상적 특징과 재발률에 관한 연구

손수빈 ( Soo Bin Son ),서수홍 ( Soo Hong Seo ),손상욱 ( Sang Wook Son ),김일환 ( Il Hwan Kim ) 대한피부과학회 2008 大韓皮膚科學會誌 Vol.46 No.1