Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid
While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in t...
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| creator | Ahrens, Jamie M Jones, James D Nieves, Nirca J Mitzey, Ann M DeLuca, Hector F Clagett-Dame, Margaret |
| description | While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth factor receptor ligand, heparin-binding epidermal growth factor-like growth factor, it does increase the expression of both amphiregulin and epigen mRNA, even after a single dose. In situ hybridization reveals an increase in these transcripts throughout the closing utricle as well as in the interfollicular epidermis. The mRNAs for other EGFR ligands including betacellulin and transforming growth factor-α, as well as the epidermal growth factor receptor are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27-dimethylene-1α,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size. |
| doi_str_mv | 10.1371/journal.pone.0188887 |
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All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth factor receptor ligand, heparin-binding epidermal growth factor-like growth factor, it does increase the expression of both amphiregulin and epigen mRNA, even after a single dose. In situ hybridization reveals an increase in these transcripts throughout the closing utricle as well as in the interfollicular epidermis. The mRNAs for other EGFR ligands including betacellulin and transforming growth factor-α, as well as the epidermal growth factor receptor are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27-dimethylene-1α,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0188887</identifier><identifier>PMID: 29182680</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Acids ; Acne ; Alfacalcidol ; Amphiregulin ; Analogs ; Analysis ; Animals ; Biochemistry ; Biology and Life Sciences ; Cages ; Calcifediol ; Dihydroxyvitamin D3 ; Dosage and administration ; Epidermal growth factor ; Epidermal growth factor receptors ; Epidermis ; Gene expression ; Genetic aspects ; Heparin ; Heparin-binding epidermal growth factor-like growth factor ; Kinases ; Ligands ; Medicine and Health Sciences ; Methylene ; Mice ; Neurosciences ; Pharmaceutical sciences ; Pharmacy ; Physical sciences ; Psoriasis ; Reduction ; Research and Analysis Methods ; Retinoic acid ; Rodents ; Skin ; Stem cells ; Thickening ; Tretinoin ; Utricle ; Vitamin D ; Vitamin D3</subject><ispartof>PloS one, 2017-11, Vol.12 (11), p.e0188887-e0188887</ispartof><rights>COPYRIGHT 2017 Public Library of Science</rights><rights>2017 Ahrens et al. 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Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size.</description><subject>Acids</subject><subject>Acne</subject><subject>Alfacalcidol</subject><subject>Amphiregulin</subject><subject>Analogs</subject><subject>Analysis</subject><subject>Animals</subject><subject>Biochemistry</subject><subject>Biology and Life Sciences</subject><subject>Cages</subject><subject>Calcifediol</subject><subject>Dihydroxyvitamin D3</subject><subject>Dosage and administration</subject><subject>Epidermal growth factor</subject><subject>Epidermal growth factor receptors</subject><subject>Epidermis</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Heparin</subject><subject>Heparin-binding epidermal growth factor-like growth factor</subject><subject>Kinases</subject><subject>Ligands</subject><subject>Medicine and Health 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activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid</title><author>Ahrens, Jamie M ; Jones, James D ; Nieves, Nirca J ; Mitzey, Ann M ; DeLuca, Hector F ; Clagett-Dame, Margaret</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-fa50ba71ebc7326476920a64ccce01fa28353c07838c1d2449ff6bcb35262c183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acids</topic><topic>Acne</topic><topic>Alfacalcidol</topic><topic>Amphiregulin</topic><topic>Analogs</topic><topic>Analysis</topic><topic>Animals</topic><topic>Biochemistry</topic><topic>Biology and Life Sciences</topic><topic>Cages</topic><topic>Calcifediol</topic><topic>Dihydroxyvitamin D3</topic><topic>Dosage and administration</topic><topic>Epidermal growth factor</topic><topic>Epidermal growth factor 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analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2017-11-28</date><risdate>2017</risdate><volume>12</volume><issue>11</issue><spage>e0188887</spage><epage>e0188887</epage><pages>e0188887-e0188887</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>While all 2-methylene-19-nor analogs of 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) tested produce an increase in epidermal thickness in the rhino mouse, only a subset reduce utricle size (comedolysis). All-trans retinoic acid (atRA) also causes epidermal thickening and a reduction in utricle size in the rhino mouse. We now report that 2-methylene-19-nor-(20S)-1α-hydroxybishomopregnacalciferol (2MbisP), a comedolytic analog, increases epidermal thickening more rapidly than does atRA, while both reduce utricle area at an equal rate. Whereas unlike atRA, 2MbisP does not alter the epidermal growth factor receptor ligand, heparin-binding epidermal growth factor-like growth factor, it does increase the expression of both amphiregulin and epigen mRNA, even after a single dose. In situ hybridization reveals an increase in these transcripts throughout the closing utricle as well as in the interfollicular epidermis. The mRNAs for other EGFR ligands including betacellulin and transforming growth factor-α, as well as the epidermal growth factor receptor are largely unaffected by 2MbisP. Another analog, 2-methylene-19-nor-(20S)-26,27-dimethylene-1α,25-dihydroxyvitamin D3 (CAGE-3), produces epidermal thickening but fails to reduce utricle size or increase AREG mRNA levels. CAGE-3 modestly increases epigen mRNA levels, but only after 5 days of dosing. Thus, 2-MbisP produces unique changes in epidermal growth factor receptor ligand mRNAs that may be responsible for both epidermal proliferation and a reduction in utricle size.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>29182680</pmid><doi>10.1371/journal.pone.0188887</doi><tpages>e0188887</tpages><orcidid>https://orcid.org/0000-0002-0364-9855</orcidid><oa>free_for_read</oa></addata></record> |
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| issn | 1932-6203 1932-6203 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry; Public Library of Science (PLoS) |
| subjects | Acids Acne Alfacalcidol Amphiregulin Analogs Analysis Animals Biochemistry Biology and Life Sciences Cages Calcifediol Dihydroxyvitamin D3 Dosage and administration Epidermal growth factor Epidermal growth factor receptors Epidermis Gene expression Genetic aspects Heparin Heparin-binding epidermal growth factor-like growth factor Kinases Ligands Medicine and Health Sciences Methylene Mice Neurosciences Pharmaceutical sciences Pharmacy Physical sciences Psoriasis Reduction Research and Analysis Methods Retinoic acid Rodents Skin Stem cells Thickening Tretinoin Utricle Vitamin D Vitamin D3 |
| title | Differential activity of 2-methylene-19-nor vitamin D analogs on growth factor gene expression in rhino mouse skin and comparison to all-trans retinoic acid |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-04T23%3A38%3A03IST&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=Differential%20activity%20of%202-methylene-19-nor%20vitamin%20D%20analogs%20on%20growth%20factor%20gene%20expression%20in%20rhino%20mouse%20skin%20and%20comparison%20to%20all-trans%20retinoic%20acid&rft.jtitle=PloS%20one&rft.au=Ahrens,%20Jamie%20M&rft.date=2017-11-28&rft.volume=12&rft.issue=11&rft.spage=e0188887&rft.epage=e0188887&rft.pages=e0188887-e0188887&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0188887&rft_dat=%3Cgale_plos_%3EA516065910%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=1969919387&rft_id=info:pmid/29182680&rft_galeid=A516065910&rft_doaj_id=oai_doaj_org_article_85cecfd3811e4ff59b622eb37af4d269&rfr_iscdi=true |