{"id":{"repo_id":"ajou","oai_identifier":"oai:repository.ajou.ac.kr:201003/13034"},"canonical_url":"https://search.dev.ndltd.org/etd/ajou/oai:repository.ajou.ac.kr:201003/13034","repository":{"repo_id":"ajou","name":"Ajou University","base_url":"http://repository.ajou.ac.kr/oai/request"},"display":{"title":"Wnt Modulators, Secreted Frizzled Related Protein (sFRP) 2 and Wnt Inhibitory Factor (WIF)-1, Stimulate Melanogenesis in Normal Human Melanocytes","abstract":"Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Previous studies showed that hyperpigmentary skins of melasma express high levels of frizzled-related protein 2 (sFRP2) and Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skins. In this study, I investigated the functional roles of sFRP2 and WIF-1 on skin pigmentation. The present study demonstrated that sFRP2 and WIF-1 were expressed in both melanocytes of normal human skin and in cultured melanocytes, suggesting that these molecules may have physiologic functions in melanocytes as an auto- or paracrine modulator of Wnt signaling. In addition, I found that secreted frizzled-related protein 2 (sFRP2) was overexpressed in the hyperpigmentary skins of not only melasma but also solar lentigo and the acutely UV-irradiated skin in vivo. Therefore, I hypothesized that sFRP2 and WIF-1 could have stimulatory roles for skin pigmentation. As results, sFRP2 and WIF-1 stimulated melanogenesis in normal human melanocytes through the increased expression of MITF and tyrosinase via β-catenin signaling. Moreover, the epidermal pigmentation of human skin was also increased in the presence of recombinant human sFRP2 and WIF-1. These findings suggest that UV irradiation may stimulate sFRP2 and WIF-1 secretion in the skin, which functions as melanogenic stimulator. This may play an important role in the development of UV-induced hyperpigmentary disorders.","abstract_html":"Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Previous studies showed that hyperpigmentary skins of melasma express high levels of frizzled-related protein 2 (sFRP2) and Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skins. In this study, I investigated the functional roles of sFRP2 and WIF-1 on skin pigmentation. The present study demonstrated that sFRP2 and WIF-1 were expressed in both melanocytes of normal human skin and in cultured melanocytes, suggesting that these molecules may have physiologic functions in melanocytes as an auto- or paracrine modulator of Wnt signaling. In addition, I found that secreted frizzled-related protein 2 (sFRP2) was overexpressed in the hyperpigmentary skins of not only melasma but also solar lentigo and the acutely UV-irradiated skin in vivo. Therefore, I hypothesized that sFRP2 and WIF-1 could have stimulatory roles for skin pigmentation. As results, sFRP2 and WIF-1 stimulated melanogenesis in normal human melanocytes through the increased expression of MITF and tyrosinase via β-catenin signaling. Moreover, the epidermal pigmentation of human skin was also increased in the presence of recombinant human sFRP2 and WIF-1. These findings suggest that UV irradiation may stimulate sFRP2 and WIF-1 secretion in the skin, which functions as melanogenic stimulator. This may play an important role in the development of UV-induced hyperpigmentary disorders.","abstract_has_math":false,"creators":["김, 미선"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["강, 희영","박, 태준","대학원 의생명과학과","110943"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2016,"date_issued":"2016-11-28","date_published":"2016-11-28","updated_at":"2026-07-24T00:51:53Z","subjects":["sFRP2","WIF-1","Hyperpigmentary disorder","Melasma","Melanocytes","Skin pigmentation"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000022841","000000022841"],"render_values":[{"text":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000022841","href":"http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000022841","code":true},{"text":"000000022841","href":null,"code":true}]}]},"links":{"outbound_url":"http://repository.ajou.ac.kr/handle/201003/13034","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["강, 희영","박, 태준","대학원 의생명과학과","110943","김, 미선"]},{"key":"dc:creator","label":"Author","values":["김, 미선"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2016-11-28","2016"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","Theses"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["sFRP2","WIF-1","Hyperpigmentary disorder","Melasma","Melanocytes","Skin pigmentation"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://repository.ajou.ac.kr/handle/201003/13034","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000022841","000000022841"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Previous studies showed that hyperpigmentary skins of melasma express high levels of frizzled-related protein 2 (sFRP2) and Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skins. In this study, I investigated the functional roles of sFRP2 and WIF-1 on skin pigmentation. The present study demonstrated that sFRP2 and WIF-1 were expressed in both melanocytes of normal human skin and in cultured melanocytes, suggesting that these molecules may have physiologic functions in melanocytes as an auto- or paracrine modulator of Wnt signaling. In addition, I found that secreted frizzled-related protein 2 (sFRP2) was overexpressed in the hyperpigmentary skins of not only melasma but also solar lentigo and the acutely UV-irradiated skin in vivo. Therefore, I hypothesized that sFRP2 and WIF-1 could have stimulatory roles for skin pigmentation. As results, sFRP2 and WIF-1 stimulated melanogenesis in normal human melanocytes through the increased expression of MITF and tyrosinase via β-catenin signaling. Moreover, the epidermal pigmentation of human skin was also increased in the presence of recombinant human sFRP2 and WIF-1. These findings suggest that UV irradiation may stimulate sFRP2 and WIF-1 secretion in the skin, which functions as melanogenic stimulator. This may play an important role in the development of UV-induced hyperpigmentary disorders.","I. INTRODUCTION 1 II. MATERIALS AND METHODS 5 A. Cell culture 5 B. Biopsy collection 5 C. Ex vivo skin organ culture and pigmentation assay in cultured skin 6 D. Melanin content and tyrosinase activity assay 7 E. Lentivirus production 7 F. RNA interference 8 G. Real-time PCR and RT-PCR 8 H. Western blot analysis 10 I. Immunohistochemistry and confocal microscopic examination 11 J. Promoter analysis 12 K. Statistical analysis 12 III. RESULTS 13 A. Secreted Frizzled-related Protein 2 (sFRP2) Functions as a Melanogenic Stimulator 13 1. sFRP2 expression is increased in UV-induced hyperpigmented skins 13 2. sFRP2 expression in skin cells 17 3. sFRP2 increases pigmentation in human melanocytes 19 4. Fibroblast-derived sFRP2 induces pigmentation in melanocytes 22 5. sFRP2 did not affect the cell proliferation in normal human melanocytes and fibroblasts 25 6. sFRP2 stimulates β-catenin signaling in normal human melanocytes 27 7. Increased expression of sFRP2 induces β-catenin translocation into nucleus 30 8. sFRP2 did not activate β-catenin signaling in normal human fibroblasts 33 B. Stimulatory effect of Wnt inhibitory factor (WIF)-1on melanogenesis 35 1. WIF-1 expression in normal human skin and melanocytes 33 2. Effect of WIF-1 upregulation on melanogenesis in melanocytes 38 3. Effect of WIF-1 downregulation on melanogenesis in melanocytes 44 4. Fibroblast-derived WIF-1 induces pigmentation in melanocytes 47 5. WIF-1 act as an antagonist of Wnt/β-catenin signaling in normal human fibroblasts 50 IV. DISCUSSION 52 V. CONCLUSION 57 Ⅵ. REFERENCES 58 국문요약 65","Doctor"]},{"key":"dc:title","label":"Title","values":["Wnt Modulators, Secreted Frizzled Related Protein (sFRP) 2 and Wnt Inhibitory Factor (WIF)-1, Stimulate Melanogenesis in Normal Human Melanocytes","인체 멜라닌 세포에서 Wnt 조절인자인 sFRP2와 WIF-1의 색소형성에 대한 역할"]}]}],"canonical_facts":{"dc:contributor":["강, 희영","박, 태준","대학원 의생명과학과","110943","김, 미선"],"dc:creator":["김, 미선"],"dc:date":["2016-11-28","2016"],"dc:description":["Wnt signaling plays a role in the differentiation as well as the development of melanocytes. Previous studies showed that hyperpigmentary skins of melasma express high levels of frizzled-related protein 2 (sFRP2) and Wnt inhibitory factor-1 (WIF-1) compared to perilesional normal skins. In this study, I investigated the functional roles of sFRP2 and WIF-1 on skin pigmentation. The present study demonstrated that sFRP2 and WIF-1 were expressed in both melanocytes of normal human skin and in cultured melanocytes, suggesting that these molecules may have physiologic functions in melanocytes as an auto- or paracrine modulator of Wnt signaling. In addition, I found that secreted frizzled-related protein 2 (sFRP2) was overexpressed in the hyperpigmentary skins of not only melasma but also solar lentigo and the acutely UV-irradiated skin in vivo. Therefore, I hypothesized that sFRP2 and WIF-1 could have stimulatory roles for skin pigmentation. As results, sFRP2 and WIF-1 stimulated melanogenesis in normal human melanocytes through the increased expression of MITF and tyrosinase via β-catenin signaling. Moreover, the epidermal pigmentation of human skin was also increased in the presence of recombinant human sFRP2 and WIF-1. These findings suggest that UV irradiation may stimulate sFRP2 and WIF-1 secretion in the skin, which functions as melanogenic stimulator. This may play an important role in the development of UV-induced hyperpigmentary disorders.","I. INTRODUCTION 1 II. MATERIALS AND METHODS 5 A. Cell culture 5 B. Biopsy collection 5 C. Ex vivo skin organ culture and pigmentation assay in cultured skin 6 D. Melanin content and tyrosinase activity assay 7 E. Lentivirus production 7 F. RNA interference 8 G. Real-time PCR and RT-PCR 8 H. Western blot analysis 10 I. Immunohistochemistry and confocal microscopic examination 11 J. Promoter analysis 12 K. Statistical analysis 12 III. RESULTS 13 A. Secreted Frizzled-related Protein 2 (sFRP2) Functions as a Melanogenic Stimulator 13 1. sFRP2 expression is increased in UV-induced hyperpigmented skins 13 2. sFRP2 expression in skin cells 17 3. sFRP2 increases pigmentation in human melanocytes 19 4. Fibroblast-derived sFRP2 induces pigmentation in melanocytes 22 5. sFRP2 did not affect the cell proliferation in normal human melanocytes and fibroblasts 25 6. sFRP2 stimulates β-catenin signaling in normal human melanocytes 27 7. Increased expression of sFRP2 induces β-catenin translocation into nucleus 30 8. sFRP2 did not activate β-catenin signaling in normal human fibroblasts 33 B. Stimulatory effect of Wnt inhibitory factor (WIF)-1on melanogenesis 35 1. WIF-1 expression in normal human skin and melanocytes 33 2. Effect of WIF-1 upregulation on melanogenesis in melanocytes 38 3. Effect of WIF-1 downregulation on melanogenesis in melanocytes 44 4. Fibroblast-derived WIF-1 induces pigmentation in melanocytes 47 5. WIF-1 act as an antagonist of Wnt/β-catenin signaling in normal human fibroblasts 50 IV. DISCUSSION 52 V. CONCLUSION 57 Ⅵ. REFERENCES 58 국문요약 65","Doctor"],"dc:identifier":["http://repository.ajou.ac.kr/handle/201003/13034","http://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000022841","000000022841"],"dc:language":["en"],"dc:subject":["sFRP2","WIF-1","Hyperpigmentary disorder","Melasma","Melanocytes","Skin pigmentation"],"dc:title":["Wnt Modulators, Secreted Frizzled Related Protein (sFRP) 2 and Wnt Inhibitory Factor (WIF)-1, Stimulate Melanogenesis in Normal Human Melanocytes","인체 멜라닌 세포에서 Wnt 조절인자인 sFRP2와 WIF-1의 색소형성에 대한 역할"],"dc:type":["Thesis","Theses"]},"updated_at":"2026-07-24T00:51:53Z"}