Brn2 is a transcription factor regulating keratinocyte differentiation with a possible role in the pathogenesis of lichen planus
Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Im...
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| creator | Shi, Ge Sohn, Kyung-Cheol Choi, Dae-Kyoung Kim, Yu-Jin Kim, Seong-Jin Ou, Bai-Sheng Piao, Yong-Jun Lee, Young Ho Yoon, Tae-Jin Lee, Young Seo, Young-Joon Kim, Chang Deok Lee, Jeung-Hoon |
| description | Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions. |
| doi_str_mv | 10.1371/journal.pone.0013216 |
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In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0013216</identifier><identifier>PMID: 20967260</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Adenovirus ; Adenoviruses ; Adipocytes ; Analysis ; Angiogenesis ; Animals ; Apoptosis ; Calcium ; Cell Biology/Gene Expression ; Cell cycle ; Cell Differentiation ; Cell growth ; Chromatin ; Dermatology ; Dermatology/Dermatologic Pathology ; Dermatology/Psoriasis and Other Inflammatory Diseases ; Development and progression ; Differentiation ; Epidermis ; Female ; Filaggrin ; Gene expression ; Genes ; Homeodomain Proteins - physiology ; Humans ; Immunoprecipitation ; Inflammation ; Keratinocytes ; Keratinocytes - cytology ; Kinases ; Lesions ; Lichen planus ; Localization ; Lymphocytes ; Lymphocytes T ; Mediation ; Medicine ; Melanoma ; Nuclei ; Nuclei (cytology) ; Pathogenesis ; POU Domain Factors - physiology ; Proteins ; Rats ; Rats, Sprague-Dawley ; Skin ; Skin diseases ; T cells ; Tissues ; Transcription factors</subject><ispartof>PloS one, 2010-10, Vol.5 (10), p.e13216-e13216</ispartof><rights>COPYRIGHT 2010 Public Library of Science</rights><rights>2010 Shi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Shi et al. 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c723t-792bb010cc2bcf905c39e5d8bf1736fedc29aa088e54936f832e5a40209f37b33</citedby><cites>FETCH-LOGICAL-c723t-792bb010cc2bcf905c39e5d8bf1736fedc29aa088e54936f832e5a40209f37b33</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953493/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2953493/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,2102,2928,23866,27924,27925,53791,53793,79600,79601</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20967260$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Schauber, Jürgen</contributor><creatorcontrib>Shi, Ge</creatorcontrib><creatorcontrib>Sohn, Kyung-Cheol</creatorcontrib><creatorcontrib>Choi, Dae-Kyoung</creatorcontrib><creatorcontrib>Kim, Yu-Jin</creatorcontrib><creatorcontrib>Kim, Seong-Jin</creatorcontrib><creatorcontrib>Ou, Bai-Sheng</creatorcontrib><creatorcontrib>Piao, Yong-Jun</creatorcontrib><creatorcontrib>Lee, Young Ho</creatorcontrib><creatorcontrib>Yoon, Tae-Jin</creatorcontrib><creatorcontrib>Lee, Young</creatorcontrib><creatorcontrib>Seo, Young-Joon</creatorcontrib><creatorcontrib>Kim, Chang Deok</creatorcontrib><creatorcontrib>Lee, Jeung-Hoon</creatorcontrib><title>Brn2 is a transcription factor regulating keratinocyte differentiation with a possible role in the pathogenesis of lichen planus</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions.</description><subject>Adenovirus</subject><subject>Adenoviruses</subject><subject>Adipocytes</subject><subject>Analysis</subject><subject>Angiogenesis</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Calcium</subject><subject>Cell Biology/Gene Expression</subject><subject>Cell cycle</subject><subject>Cell Differentiation</subject><subject>Cell growth</subject><subject>Chromatin</subject><subject>Dermatology</subject><subject>Dermatology/Dermatologic Pathology</subject><subject>Dermatology/Psoriasis and Other Inflammatory Diseases</subject><subject>Development and progression</subject><subject>Differentiation</subject><subject>Epidermis</subject><subject>Female</subject><subject>Filaggrin</subject><subject>Gene expression</subject><subject>Genes</subject><subject>Homeodomain Proteins - physiology</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Inflammation</subject><subject>Keratinocytes</subject><subject>Keratinocytes - cytology</subject><subject>Kinases</subject><subject>Lesions</subject><subject>Lichen planus</subject><subject>Localization</subject><subject>Lymphocytes</subject><subject>Lymphocytes T</subject><subject>Mediation</subject><subject>Medicine</subject><subject>Melanoma</subject><subject>Nuclei</subject><subject>Nuclei (cytology)</subject><subject>Pathogenesis</subject><subject>POU Domain Factors - physiology</subject><subject>Proteins</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Skin</subject><subject>Skin diseases</subject><subject>T cells</subject><subject>Tissues</subject><subject>Transcription 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Jürgen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Brn2 is a transcription factor regulating keratinocyte differentiation with a possible role in the pathogenesis of lichen planus</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2010-10-12</date><risdate>2010</risdate><volume>5</volume><issue>10</issue><spage>e13216</spage><epage>e13216</epage><pages>e13216-e13216</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Terminal differentiation of skin keratinocytes is a vertically directed multi-step process that is tightly controlled by the sequential expression of a variety of genes. In this study, we investigated the role of the POU domain-containing transcription factor Brn2 in keratinocyte differentiation. Immunohistochemical analysis showed that Brn2 is expressed primarily in the upper granular layer. Consistent with its epidermal localization, Brn2 expression was highly induced at 14 days after calcium treatment of cultured normal human epidermal keratinocytes. When Brn2 was overexpressed by adenoviral transduction, Brn2 led to increased expression of the differentiation-related genes involucrin, filaggrin, and loricrin in addition to inhibition of their proliferation. Chromatin immunoprecipitation demonstrated that Brn2 bound to the promoter regions of these differentiation-related genes. We injected the purified Brn2 adenovirus into rat skin, which led to a thickened epidermis with increased amounts of differentiation related markers. The histopathologic features of adenovirus-Brn2 injected skin tissues looked similar to the features of lichen planus, a human skin disease showing chronic inflammation and well-differentiated epidermal changes. Moreover, Brn2 is shown to be expressed in almost all cell nuclei of the thickened epidermis of lichen planus, and Brn2 also attracts T lymphocytes. Our results demonstrate that Brn2 is probably a transcriptional factor playing an important role in keratinocyte differentiation and probably also in the pathogenesis of lichen planus lesions.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>20967260</pmid><doi>10.1371/journal.pone.0013216</doi><tpages>e13216</tpages><oa>free_for_read</oa></addata></record> |
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| recordid | cdi_plos_journals_1295463789 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Adenovirus Adenoviruses Adipocytes Analysis Angiogenesis Animals Apoptosis Calcium Cell Biology/Gene Expression Cell cycle Cell Differentiation Cell growth Chromatin Dermatology Dermatology/Dermatologic Pathology Dermatology/Psoriasis and Other Inflammatory Diseases Development and progression Differentiation Epidermis Female Filaggrin Gene expression Genes Homeodomain Proteins - physiology Humans Immunoprecipitation Inflammation Keratinocytes Keratinocytes - cytology Kinases Lesions Lichen planus Localization Lymphocytes Lymphocytes T Mediation Medicine Melanoma Nuclei Nuclei (cytology) Pathogenesis POU Domain Factors - physiology Proteins Rats Rats, Sprague-Dawley Skin Skin diseases T cells Tissues Transcription factors |
| title | Brn2 is a transcription factor regulating keratinocyte differentiation with a possible role in the pathogenesis of lichen planus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-05T11%3A06%3A55IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Brn2%20is%20a%20transcription%20factor%20regulating%20keratinocyte%20differentiation%20with%20a%20possible%20role%20in%20the%20pathogenesis%20of%20lichen%20planus&rft.jtitle=PloS%20one&rft.au=Shi,%20Ge&rft.date=2010-10-12&rft.volume=5&rft.issue=10&rft.spage=e13216&rft.epage=e13216&rft.pages=e13216-e13216&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0013216&rft_dat=%3Cgale_plos_%3EA473855535%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1295463789&rft_id=info:pmid/20967260&rft_galeid=A473855535&rft_doaj_id=oai_doaj_org_article_cf4c8f3720524c41a65ab77e0ef1c80a&rfr_iscdi=true |