Peroxisome-Proliferator-Activated Receptor (PPAR)-γ Activation Stimulates Keratinocyte Differentiation
Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-α or PPAR-δ activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-γ a...
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| Veröffentlicht in: | Journal of investigative dermatology 2004-08, Vol.123 (2), p.305-312 |
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| creator | Mao-Qiang, Man Fowler, Ashley J. Schmuth, Matthias Lau, Peggy Chang, Sandra Brown, Barbara E. Moser, Arthur H. Michalik, Liliane Desvergne, Beatrice Wahli, Walter Li, Mei Metzger, Daniel Chambon, Pierre H. Elias, Peter M. Feingold, Kenneth R. |
| description | Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-α or PPAR-δ activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-γ activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-γ activation stimulates keratinocyte differentiation. Additionally, PPAR-γ activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-γ activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-γ activators are mediated by PPAR-γ, we next examined animals deficient in PPAR-γ. Mice with a deficiency of PPAR-γ specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-γ-deficient epidermis. Although PPAR-γ activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-γ-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-γ activators is mediated by PPAR-γ. In contrast, PPAR-γ activators inhibited inflammation in both PPAR-γ-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-γ activators does not require PPAR-γ in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-γ activators maybe useful in the treatment of cutaneous disorders. |
| doi_str_mv | 10.1111/j.0022-202X.2004.23235.x |
| format | Article |
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Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-γ activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-γ activation stimulates keratinocyte differentiation. Additionally, PPAR-γ activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-γ activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-γ activators are mediated by PPAR-γ, we next examined animals deficient in PPAR-γ. Mice with a deficiency of PPAR-γ specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-γ-deficient epidermis. Although PPAR-γ activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-γ-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-γ activators is mediated by PPAR-γ. In contrast, PPAR-γ activators inhibited inflammation in both PPAR-γ-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-γ activators does not require PPAR-γ in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-γ activators maybe useful in the treatment of cutaneous disorders.</description><identifier>ISSN: 0022-202X</identifier><identifier>EISSN: 1523-1747</identifier><identifier>DOI: 10.1111/j.0022-202X.2004.23235.x</identifier><identifier>PMID: 15245430</identifier><identifier>CODEN: JIDEAE</identifier><language>eng</language><publisher>Danvers, MA: Elsevier Inc</publisher><subject>Animals ; Biological and medical sciences ; Cell Differentiation - drug effects ; Cell Differentiation - physiology ; Dermatitis, Irritant - drug therapy ; Dermatitis, Irritant - metabolism ; Dermatitis, Irritant - pathology ; Dermatology ; Epidermis - pathology ; Female ; Filaggrin Proteins ; Homeostasis - drug effects ; Homeostasis - physiology ; Hypoglycemic Agents - pharmacology ; inflammation ; Keratinocytes - cytology ; Keratinocytes - drug effects ; Keratinocytes - metabolism ; Life Sciences ; Male ; Medical sciences ; Mice ; Mice, Hairless ; Mice, Transgenic ; nuclear hormone receptor ; permeability barrier function ; Protein Precursors - genetics ; Receptors, Cytoplasmic and Nuclear - agonists ; Receptors, Cytoplasmic and Nuclear - genetics ; Receptors, Cytoplasmic and Nuclear - metabolism ; RNA, Messenger - analysis ; stratum corneum ; Thiazolidinediones - pharmacology ; Transcription Factors - agonists ; Transcription Factors - genetics ; Transcription Factors - metabolism ; Transglutaminases - genetics</subject><ispartof>Journal of investigative dermatology, 2004-08, Vol.123 (2), p.305-312</ispartof><rights>2004 The Society for Investigative Dermatology, Inc</rights><rights>2004 INIST-CNRS</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c561t-bdcc40587e3c1ea98b1c0f50fb35968e2f5530199c899f534be093acbc78d85d3</citedby><cites>FETCH-LOGICAL-c561t-bdcc40587e3c1ea98b1c0f50fb35968e2f5530199c899f534be093acbc78d85d3</cites><orcidid>0000-0002-5555-046X ; 0000-0003-4225-6699 ; 0000-0002-5966-9089</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925,64387</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16060677$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15245430$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://hal.science/hal-03311493$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Mao-Qiang, Man</creatorcontrib><creatorcontrib>Fowler, Ashley J.</creatorcontrib><creatorcontrib>Schmuth, Matthias</creatorcontrib><creatorcontrib>Lau, Peggy</creatorcontrib><creatorcontrib>Chang, Sandra</creatorcontrib><creatorcontrib>Brown, Barbara E.</creatorcontrib><creatorcontrib>Moser, Arthur H.</creatorcontrib><creatorcontrib>Michalik, Liliane</creatorcontrib><creatorcontrib>Desvergne, Beatrice</creatorcontrib><creatorcontrib>Wahli, Walter</creatorcontrib><creatorcontrib>Li, Mei</creatorcontrib><creatorcontrib>Metzger, Daniel</creatorcontrib><creatorcontrib>Chambon, Pierre H.</creatorcontrib><creatorcontrib>Elias, Peter M.</creatorcontrib><creatorcontrib>Feingold, Kenneth R.</creatorcontrib><title>Peroxisome-Proliferator-Activated Receptor (PPAR)-γ Activation Stimulates Keratinocyte Differentiation</title><title>Journal of investigative dermatology</title><addtitle>J Invest Dermatol</addtitle><description>Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-α or PPAR-δ activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. 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Mice with a deficiency of PPAR-γ specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-γ-deficient epidermis. Although PPAR-γ activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-γ-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-γ activators is mediated by PPAR-γ. In contrast, PPAR-γ activators inhibited inflammation in both PPAR-γ-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-γ activators does not require PPAR-γ in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-γ activators maybe useful in the treatment of cutaneous disorders.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Differentiation - drug effects</subject><subject>Cell Differentiation - physiology</subject><subject>Dermatitis, Irritant - drug therapy</subject><subject>Dermatitis, Irritant - metabolism</subject><subject>Dermatitis, Irritant - pathology</subject><subject>Dermatology</subject><subject>Epidermis - pathology</subject><subject>Female</subject><subject>Filaggrin Proteins</subject><subject>Homeostasis - drug effects</subject><subject>Homeostasis - physiology</subject><subject>Hypoglycemic Agents - pharmacology</subject><subject>inflammation</subject><subject>Keratinocytes - cytology</subject><subject>Keratinocytes - drug effects</subject><subject>Keratinocytes - metabolism</subject><subject>Life Sciences</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Hairless</subject><subject>Mice, Transgenic</subject><subject>nuclear hormone receptor</subject><subject>permeability barrier function</subject><subject>Protein Precursors - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - agonists</subject><subject>Receptors, Cytoplasmic and Nuclear - genetics</subject><subject>Receptors, Cytoplasmic and Nuclear - metabolism</subject><subject>RNA, Messenger - analysis</subject><subject>stratum corneum</subject><subject>Thiazolidinediones - pharmacology</subject><subject>Transcription Factors - agonists</subject><subject>Transcription Factors - genetics</subject><subject>Transcription Factors - metabolism</subject><subject>Transglutaminases - genetics</subject><issn>0022-202X</issn><issn>1523-1747</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc2O0zAUhS0EYkrhEUDZgJhFgn_iJF6W4WcQlagGkNhZjnMDrpK42E7VeS7eg2fCmUSdJdcLS_d-59i6B6GE4IzEerPPMKY0pZj-yCjGeUYZZTw7PUArwilLSZmXD9HqDF2gJ97vMSZFzqvH6CJCOc8ZXqGfO3D2ZLztId0525kWnArWpRsdzFEFaJIb0HCIreT1bre5uUz__kmWobFD8jWYfuwi6JPPk9QMVt8GSN6ZNlrBEMwd9xQ9alXn4dlyr9H3D--_XV2n2y8fP11ttqnmBQlp3WidY16VwDQBJaqaaNxy3NaMi6IC2nLOMBFCV0K0nOU1YMGUrnVZNRVv2Bpdzr6_VCcPzvTK3UqrjLzebOXUw4wRkgt2JJF9NbMHZ3-P4IPsjdfQdWoAO3pZFIUoWaw1qmZQO-u9g_bsTLCcApF7Oe1aTruWUyDyLhB5itIXyxtj3UNzL1wSiMDLBVBeq651atDG33MFjqcsI_d85gYVRgdngBeY5ozH-dt5DnG7RwNOem1g0NAYBzrIxpr___YfN5O0qQ</recordid><startdate>20040801</startdate><enddate>20040801</enddate><creator>Mao-Qiang, Man</creator><creator>Fowler, Ashley J.</creator><creator>Schmuth, Matthias</creator><creator>Lau, Peggy</creator><creator>Chang, Sandra</creator><creator>Brown, Barbara E.</creator><creator>Moser, Arthur H.</creator><creator>Michalik, Liliane</creator><creator>Desvergne, Beatrice</creator><creator>Wahli, Walter</creator><creator>Li, Mei</creator><creator>Metzger, Daniel</creator><creator>Chambon, Pierre H.</creator><creator>Elias, Peter M.</creator><creator>Feingold, Kenneth R.</creator><general>Elsevier Inc</general><general>Nature Publishing</general><general>Nature Publishing Group</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>1XC</scope><orcidid>https://orcid.org/0000-0002-5555-046X</orcidid><orcidid>https://orcid.org/0000-0003-4225-6699</orcidid><orcidid>https://orcid.org/0000-0002-5966-9089</orcidid></search><sort><creationdate>20040801</creationdate><title>Peroxisome-Proliferator-Activated Receptor (PPAR)-γ Activation Stimulates Keratinocyte Differentiation</title><author>Mao-Qiang, Man ; Fowler, Ashley J. ; Schmuth, Matthias ; Lau, Peggy ; Chang, Sandra ; Brown, Barbara E. ; Moser, Arthur H. ; Michalik, Liliane ; Desvergne, Beatrice ; Wahli, Walter ; Li, Mei ; Metzger, Daniel ; Chambon, Pierre H. ; Elias, Peter M. ; Feingold, Kenneth R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c561t-bdcc40587e3c1ea98b1c0f50fb35968e2f5530199c899f534be093acbc78d85d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Differentiation - drug effects</topic><topic>Cell Differentiation - physiology</topic><topic>Dermatitis, Irritant - drug therapy</topic><topic>Dermatitis, Irritant - metabolism</topic><topic>Dermatitis, Irritant - pathology</topic><topic>Dermatology</topic><topic>Epidermis - pathology</topic><topic>Female</topic><topic>Filaggrin Proteins</topic><topic>Homeostasis - drug effects</topic><topic>Homeostasis - physiology</topic><topic>Hypoglycemic Agents - pharmacology</topic><topic>inflammation</topic><topic>Keratinocytes - cytology</topic><topic>Keratinocytes - drug effects</topic><topic>Keratinocytes - metabolism</topic><topic>Life Sciences</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Hairless</topic><topic>Mice, Transgenic</topic><topic>nuclear hormone receptor</topic><topic>permeability barrier function</topic><topic>Protein Precursors - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - agonists</topic><topic>Receptors, Cytoplasmic and Nuclear - genetics</topic><topic>Receptors, Cytoplasmic and Nuclear - metabolism</topic><topic>RNA, Messenger - analysis</topic><topic>stratum corneum</topic><topic>Thiazolidinediones - pharmacology</topic><topic>Transcription Factors - agonists</topic><topic>Transcription Factors - genetics</topic><topic>Transcription Factors - metabolism</topic><topic>Transglutaminases - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mao-Qiang, Man</creatorcontrib><creatorcontrib>Fowler, Ashley J.</creatorcontrib><creatorcontrib>Schmuth, Matthias</creatorcontrib><creatorcontrib>Lau, Peggy</creatorcontrib><creatorcontrib>Chang, Sandra</creatorcontrib><creatorcontrib>Brown, Barbara E.</creatorcontrib><creatorcontrib>Moser, Arthur H.</creatorcontrib><creatorcontrib>Michalik, Liliane</creatorcontrib><creatorcontrib>Desvergne, Beatrice</creatorcontrib><creatorcontrib>Wahli, Walter</creatorcontrib><creatorcontrib>Li, Mei</creatorcontrib><creatorcontrib>Metzger, Daniel</creatorcontrib><creatorcontrib>Chambon, Pierre H.</creatorcontrib><creatorcontrib>Elias, Peter M.</creatorcontrib><creatorcontrib>Feingold, Kenneth R.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><jtitle>Journal of investigative dermatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mao-Qiang, Man</au><au>Fowler, Ashley J.</au><au>Schmuth, Matthias</au><au>Lau, Peggy</au><au>Chang, Sandra</au><au>Brown, Barbara E.</au><au>Moser, Arthur H.</au><au>Michalik, Liliane</au><au>Desvergne, Beatrice</au><au>Wahli, Walter</au><au>Li, Mei</au><au>Metzger, Daniel</au><au>Chambon, Pierre H.</au><au>Elias, Peter M.</au><au>Feingold, Kenneth R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Peroxisome-Proliferator-Activated Receptor (PPAR)-γ Activation Stimulates Keratinocyte Differentiation</atitle><jtitle>Journal of investigative dermatology</jtitle><addtitle>J Invest Dermatol</addtitle><date>2004-08-01</date><risdate>2004</risdate><volume>123</volume><issue>2</issue><spage>305</spage><epage>312</epage><pages>305-312</pages><issn>0022-202X</issn><eissn>1523-1747</eissn><coden>JIDEAE</coden><abstract>Previous studies demonstrated that peroxisome-proliferator-activated receptor (PPAR)-α or PPAR-δ activation stimulates keratinocyte differentiation, is anti-inflammatory, and improves barrier homeostasis. Here we demonstrate that treatment of cultured human keratinocytes with ciglitazone, a PPAR-γ activator, increases involucrin and transglutaminase 1 mRNA levels. Moreover, topical treatment of hairless mice with ciglitazone or troglitazone increases loricrin, involucrin, and filaggrin expression without altering epidermal morphology. These results indicate that PPAR-γ activation stimulates keratinocyte differentiation. Additionally, PPAR-γ activators accelerated barrier recovery following acute disruption by either tape stripping or acetone treatment, indicating an improvement in permeability barrier homeostasis. Treatment with PPAR-γ activators also reduced the cutaneous inflammatory response that is induced by phorbol 12-myristate-13-acetate, a model of irritant contact dermatitis and oxazolone, a model of allergic contact dermatitis. To determine whether the effects of PPAR-γ activators are mediated by PPAR-γ, we next examined animals deficient in PPAR-γ. Mice with a deficiency of PPAR-γ specifically localized to the epidermis did not display any cutaneous abnormalites on inspection, but on light microscopy there was a modest increase in epidermal thickness associated with an increase in proliferating cell nuclear antigen (PCNA) staining. Key functions of the skin including permeability barrier homeostasis, stratum corneum surface pH, and water-holding capacity, and response to inflammatory stimuli were not altered in PPAR-γ-deficient epidermis. Although PPAR-γ activators stimulated loricrin and filaggrin expression in wild-type animals, however, in PPAR-γ-deficient mice no effect was observed indicating that the stimulation of differentiation by PPAR-γ activators is mediated by PPAR-γ. In contrast, PPAR-γ activators inhibited inflammation in both PPAR-γ-deficient and wild-type mouse skin, indicating that the inhibition of cutaneous inflammation by these PPAR-γ activators does not require PPAR-γ in keratinocytes. These observations suggest that thiazolidindiones and perhaps other PPAR-γ activators maybe useful in the treatment of cutaneous disorders.</abstract><cop>Danvers, MA</cop><pub>Elsevier Inc</pub><pmid>15245430</pmid><doi>10.1111/j.0022-202X.2004.23235.x</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-5555-046X</orcidid><orcidid>https://orcid.org/0000-0003-4225-6699</orcidid><orcidid>https://orcid.org/0000-0002-5966-9089</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of investigative dermatology, 2004-08, Vol.123 (2), p.305-312 |
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| language | eng |
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| source | MEDLINE; EZB-FREE-00999 freely available EZB journals; ProQuest Central UK/Ireland; Alma/SFX Local Collection |
| subjects | Animals Biological and medical sciences Cell Differentiation - drug effects Cell Differentiation - physiology Dermatitis, Irritant - drug therapy Dermatitis, Irritant - metabolism Dermatitis, Irritant - pathology Dermatology Epidermis - pathology Female Filaggrin Proteins Homeostasis - drug effects Homeostasis - physiology Hypoglycemic Agents - pharmacology inflammation Keratinocytes - cytology Keratinocytes - drug effects Keratinocytes - metabolism Life Sciences Male Medical sciences Mice Mice, Hairless Mice, Transgenic nuclear hormone receptor permeability barrier function Protein Precursors - genetics Receptors, Cytoplasmic and Nuclear - agonists Receptors, Cytoplasmic and Nuclear - genetics Receptors, Cytoplasmic and Nuclear - metabolism RNA, Messenger - analysis stratum corneum Thiazolidinediones - pharmacology Transcription Factors - agonists Transcription Factors - genetics Transcription Factors - metabolism Transglutaminases - genetics |
| title | Peroxisome-Proliferator-Activated Receptor (PPAR)-γ Activation Stimulates Keratinocyte Differentiation |
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