Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma
Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma. Using skin from patients and healthy donors, the expression of perio...
Gespeichert in:
| Veröffentlicht in: | PloS one 2012-07, Vol.7 (7), p.e41994 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 7 |
| container_start_page | e41994 |
| container_title | PloS one |
| container_volume | 7 |
| creator | Yang, Lingli Serada, Satoshi Fujimoto, Minoru Terao, Mika Kotobuki, Yorihisa Kitaba, Shun Matsui, Saki Kudo, Akira Naka, Tetsuji Murota, Hiroyuki Katayama, Ichiro |
| description | Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma.
Using skin from patients and healthy donors, the expression of periostin was assessed by immunohistochemistry and immunoblotting analyses. Furthermore, we investigated periostin(-/-) (PN(-/-)) and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate-buffered saline. Bleomycin-induced fibrotic changes were compared in PN(-/-) and WT mice by histological analysis as well as by measurements of profibrotic cytokine and extracellular matrix protein expression levels in vivo and in vitro. To determine the downstream pathway involved in periostin signaling, receptor neutralizing antibody and signal transduction inhibitors were used in vitro.
Elevated expression of periostin was observed in the lesional skin of patients with scleroderma compared with healthy donors. Although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased numbers of myofibroblasts after bleomycin treatment, PN(-/-) mice showed resistance to these changes. In vitro, dermal fibroblasts from PN(-/-) mice showed reduced transcript expression of alpha smooth actin and procollagen type-I alpha 1 (Col1α1) induced by transforming growth factor beta 1 (TGFβ1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by blocking the αv integrin-mediated PI3K/Akt signaling either with anti-αv functional blocking antibody or with the PI3K/Akt kinase inhibitor LY294002.
Periostin plays an essential role in the pathogenesis of Bleomycin-induced scleroderma in mice. Periostin may represent a potential therapeutic target for human scleroderma. |
| doi_str_mv | 10.1371/journal.pone.0041994 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_plos_</sourceid><recordid>TN_cdi_plos_journals_1327116329</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A477045873</galeid><doaj_id>oai_doaj_org_article_82f7587fad8043158cfb181170e30bac</doaj_id><sourcerecordid>A477045873</sourcerecordid><originalsourceid>FETCH-LOGICAL-c758t-a62a1f65116d1006521f11369ff01df2e926205503b25d99b83a333d0afee6173</originalsourceid><addsrcrecordid>eNqNkm2L1DAUhYso7rr6D0QLguCHmc1N-vpFGBZfBhd28e1ruNPczGS2bcYkXfTfm3G6yxQUpNCG2-ec3h5OkjwHNgdRwvnWDq7Hdr6zPc0Zy6CuswfJKdSCzwrOxMOj80nyxPstY7moiuJxcsJ5DVCV7DSha3LG-mD6VGNjWhMwkE_9TRz4piVnvfHprcH0eik-nS9uQqpoR72iPqQdNRvsje_SSGPa2cFTvCtqU6tHuSLX4dPkkcbW07PxeZZ8e__u68XH2eXVh-XF4nLWlHkVZlhwBF3kAIUCxoqcgwYQRa01A6U51Tz-TZ4zseK5qutVJVAIoRhqogJKcZa8PPjuWuvlmJCXIHgZPQWvI7E8EMriVu6c6dD9khaN_DOwbi3RBRNXlxXXcatSo6pYJiCvGr2CCqBkJNgKm-j1dvzasOpINTESh-3EdPqmNxu5trdSZCxjXESDV6OBsz8G8uEfK4_UGuNWptc2mjWd8Y1cZGXJsrjk3mv-FypeijrTxI5oE-cTwZuJIDKBfoY1Dt7L5ZfP_89efZ-yr4_YDWEbNt62QzC291MwO4BNLJl3pO-TAyb3Fb9LQ-4rLseKR9mL49TvRXedFr8BHnv1ZQ</addsrcrecordid><sourcetype>Open Website</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1327116329</pqid></control><display><type>article</type><title>Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma</title><source>Public Library of Science (PLoS) Journals Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Yang, Lingli ; Serada, Satoshi ; Fujimoto, Minoru ; Terao, Mika ; Kotobuki, Yorihisa ; Kitaba, Shun ; Matsui, Saki ; Kudo, Akira ; Naka, Tetsuji ; Murota, Hiroyuki ; Katayama, Ichiro</creator><contributor>Rossini, Alessandra</contributor><creatorcontrib>Yang, Lingli ; Serada, Satoshi ; Fujimoto, Minoru ; Terao, Mika ; Kotobuki, Yorihisa ; Kitaba, Shun ; Matsui, Saki ; Kudo, Akira ; Naka, Tetsuji ; Murota, Hiroyuki ; Katayama, Ichiro ; Rossini, Alessandra</creatorcontrib><description>Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma.
Using skin from patients and healthy donors, the expression of periostin was assessed by immunohistochemistry and immunoblotting analyses. Furthermore, we investigated periostin(-/-) (PN(-/-)) and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate-buffered saline. Bleomycin-induced fibrotic changes were compared in PN(-/-) and WT mice by histological analysis as well as by measurements of profibrotic cytokine and extracellular matrix protein expression levels in vivo and in vitro. To determine the downstream pathway involved in periostin signaling, receptor neutralizing antibody and signal transduction inhibitors were used in vitro.
Elevated expression of periostin was observed in the lesional skin of patients with scleroderma compared with healthy donors. Although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased numbers of myofibroblasts after bleomycin treatment, PN(-/-) mice showed resistance to these changes. In vitro, dermal fibroblasts from PN(-/-) mice showed reduced transcript expression of alpha smooth actin and procollagen type-I alpha 1 (Col1α1) induced by transforming growth factor beta 1 (TGFβ1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by blocking the αv integrin-mediated PI3K/Akt signaling either with anti-αv functional blocking antibody or with the PI3K/Akt kinase inhibitor LY294002.
Periostin plays an essential role in the pathogenesis of Bleomycin-induced scleroderma in mice. Periostin may represent a potential therapeutic target for human scleroderma.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0041994</identifier><identifier>PMID: 22911870</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>1-Phosphatidylinositol 3-kinase ; Actin ; Adult ; Aged ; AKT protein ; Analysis ; Animals ; Antibodies ; Arthritis ; Asthma ; Biology ; Bleomycin ; Blocking antibodies ; Cell adhesion & migration ; Cell Adhesion Molecules - metabolism ; Cell Differentiation - drug effects ; Cellular signal transduction ; Collagen ; Collagen Type I - metabolism ; Cytokines ; Dermatology ; Disease ; Disease Models, Animal ; Enzyme inhibitors ; Extracellular matrix ; Extracellular Matrix Proteins - metabolism ; Female ; Fibroblasts ; Fibrosis ; Gene Knockout Techniques ; Growth factors ; Heart attacks ; Humans ; Immunoblotting ; Immunohistochemistry ; In vivo methods and tests ; Integrin alphaV - metabolism ; Integrins ; Laboratories ; Male ; Matrix protein ; Medical research ; Medicine ; Mice ; Middle Aged ; Myofibroblasts - drug effects ; Myofibroblasts - metabolism ; Myofibroblasts - pathology ; Pathogenesis ; Patients ; Phosphates ; Phosphatidylinositol 3-Kinases - metabolism ; Procollagen ; Proteins ; Proto-Oncogene Proteins c-akt - metabolism ; Rodents ; Scleroderma ; Scleroderma (Disease) ; Scleroderma, Systemic - enzymology ; Scleroderma, Systemic - pathology ; Sclerosis ; Signal transduction ; Signaling ; Skin ; Skin - drug effects ; Skin - pathology ; Skin diseases ; Transcription ; Transduction ; Transforming Growth Factor beta1 - pharmacology ; Transforming growth factor-b1 ; Transforming growth factors ; Tumor necrosis factor-TNF ; University graduates ; Up-Regulation - drug effects ; Wound healing ; Young Adult</subject><ispartof>PloS one, 2012-07, Vol.7 (7), p.e41994</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Yang 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>Yang et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c758t-a62a1f65116d1006521f11369ff01df2e926205503b25d99b83a333d0afee6173</citedby><cites>FETCH-LOGICAL-c758t-a62a1f65116d1006521f11369ff01df2e926205503b25d99b83a333d0afee6173</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/PMC3404023/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3404023/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79343,79344</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22911870$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rossini, Alessandra</contributor><creatorcontrib>Yang, Lingli</creatorcontrib><creatorcontrib>Serada, Satoshi</creatorcontrib><creatorcontrib>Fujimoto, Minoru</creatorcontrib><creatorcontrib>Terao, Mika</creatorcontrib><creatorcontrib>Kotobuki, Yorihisa</creatorcontrib><creatorcontrib>Kitaba, Shun</creatorcontrib><creatorcontrib>Matsui, Saki</creatorcontrib><creatorcontrib>Kudo, Akira</creatorcontrib><creatorcontrib>Naka, Tetsuji</creatorcontrib><creatorcontrib>Murota, Hiroyuki</creatorcontrib><creatorcontrib>Katayama, Ichiro</creatorcontrib><title>Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma.
Using skin from patients and healthy donors, the expression of periostin was assessed by immunohistochemistry and immunoblotting analyses. Furthermore, we investigated periostin(-/-) (PN(-/-)) and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate-buffered saline. Bleomycin-induced fibrotic changes were compared in PN(-/-) and WT mice by histological analysis as well as by measurements of profibrotic cytokine and extracellular matrix protein expression levels in vivo and in vitro. To determine the downstream pathway involved in periostin signaling, receptor neutralizing antibody and signal transduction inhibitors were used in vitro.
Elevated expression of periostin was observed in the lesional skin of patients with scleroderma compared with healthy donors. Although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased numbers of myofibroblasts after bleomycin treatment, PN(-/-) mice showed resistance to these changes. In vitro, dermal fibroblasts from PN(-/-) mice showed reduced transcript expression of alpha smooth actin and procollagen type-I alpha 1 (Col1α1) induced by transforming growth factor beta 1 (TGFβ1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by blocking the αv integrin-mediated PI3K/Akt signaling either with anti-αv functional blocking antibody or with the PI3K/Akt kinase inhibitor LY294002.
Periostin plays an essential role in the pathogenesis of Bleomycin-induced scleroderma in mice. Periostin may represent a potential therapeutic target for human scleroderma.</description><subject>1-Phosphatidylinositol 3-kinase</subject><subject>Actin</subject><subject>Adult</subject><subject>Aged</subject><subject>AKT protein</subject><subject>Analysis</subject><subject>Animals</subject><subject>Antibodies</subject><subject>Arthritis</subject><subject>Asthma</subject><subject>Biology</subject><subject>Bleomycin</subject><subject>Blocking antibodies</subject><subject>Cell adhesion & migration</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Cell Differentiation - drug effects</subject><subject>Cellular signal transduction</subject><subject>Collagen</subject><subject>Collagen Type I - metabolism</subject><subject>Cytokines</subject><subject>Dermatology</subject><subject>Disease</subject><subject>Disease Models, Animal</subject><subject>Enzyme inhibitors</subject><subject>Extracellular matrix</subject><subject>Extracellular Matrix Proteins - metabolism</subject><subject>Female</subject><subject>Fibroblasts</subject><subject>Fibrosis</subject><subject>Gene Knockout Techniques</subject><subject>Growth factors</subject><subject>Heart attacks</subject><subject>Humans</subject><subject>Immunoblotting</subject><subject>Immunohistochemistry</subject><subject>In vivo methods and tests</subject><subject>Integrin alphaV - metabolism</subject><subject>Integrins</subject><subject>Laboratories</subject><subject>Male</subject><subject>Matrix protein</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Mice</subject><subject>Middle Aged</subject><subject>Myofibroblasts - drug effects</subject><subject>Myofibroblasts - metabolism</subject><subject>Myofibroblasts - pathology</subject><subject>Pathogenesis</subject><subject>Patients</subject><subject>Phosphates</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Procollagen</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-akt - metabolism</subject><subject>Rodents</subject><subject>Scleroderma</subject><subject>Scleroderma (Disease)</subject><subject>Scleroderma, Systemic - enzymology</subject><subject>Scleroderma, Systemic - pathology</subject><subject>Sclerosis</subject><subject>Signal transduction</subject><subject>Signaling</subject><subject>Skin</subject><subject>Skin - drug effects</subject><subject>Skin - pathology</subject><subject>Skin diseases</subject><subject>Transcription</subject><subject>Transduction</subject><subject>Transforming Growth Factor beta1 - pharmacology</subject><subject>Transforming growth factor-b1</subject><subject>Transforming growth factors</subject><subject>Tumor necrosis factor-TNF</subject><subject>University graduates</subject><subject>Up-Regulation - drug effects</subject><subject>Wound healing</subject><subject>Young Adult</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkm2L1DAUhYso7rr6D0QLguCHmc1N-vpFGBZfBhd28e1ruNPczGS2bcYkXfTfm3G6yxQUpNCG2-ec3h5OkjwHNgdRwvnWDq7Hdr6zPc0Zy6CuswfJKdSCzwrOxMOj80nyxPstY7moiuJxcsJ5DVCV7DSha3LG-mD6VGNjWhMwkE_9TRz4piVnvfHprcH0eik-nS9uQqpoR72iPqQdNRvsje_SSGPa2cFTvCtqU6tHuSLX4dPkkcbW07PxeZZ8e__u68XH2eXVh-XF4nLWlHkVZlhwBF3kAIUCxoqcgwYQRa01A6U51Tz-TZ4zseK5qutVJVAIoRhqogJKcZa8PPjuWuvlmJCXIHgZPQWvI7E8EMriVu6c6dD9khaN_DOwbi3RBRNXlxXXcatSo6pYJiCvGr2CCqBkJNgKm-j1dvzasOpINTESh-3EdPqmNxu5trdSZCxjXESDV6OBsz8G8uEfK4_UGuNWptc2mjWd8Y1cZGXJsrjk3mv-FypeijrTxI5oE-cTwZuJIDKBfoY1Dt7L5ZfP_89efZ-yr4_YDWEbNt62QzC291MwO4BNLJl3pO-TAyb3Fb9LQ-4rLseKR9mL49TvRXedFr8BHnv1ZQ</recordid><startdate>20120724</startdate><enddate>20120724</enddate><creator>Yang, Lingli</creator><creator>Serada, Satoshi</creator><creator>Fujimoto, Minoru</creator><creator>Terao, Mika</creator><creator>Kotobuki, Yorihisa</creator><creator>Kitaba, Shun</creator><creator>Matsui, Saki</creator><creator>Kudo, Akira</creator><creator>Naka, Tetsuji</creator><creator>Murota, Hiroyuki</creator><creator>Katayama, Ichiro</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120724</creationdate><title>Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma</title><author>Yang, Lingli ; Serada, Satoshi ; Fujimoto, Minoru ; Terao, Mika ; Kotobuki, Yorihisa ; Kitaba, Shun ; Matsui, Saki ; Kudo, Akira ; Naka, Tetsuji ; Murota, Hiroyuki ; Katayama, Ichiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c758t-a62a1f65116d1006521f11369ff01df2e926205503b25d99b83a333d0afee6173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1-Phosphatidylinositol 3-kinase</topic><topic>Actin</topic><topic>Adult</topic><topic>Aged</topic><topic>AKT protein</topic><topic>Analysis</topic><topic>Animals</topic><topic>Antibodies</topic><topic>Arthritis</topic><topic>Asthma</topic><topic>Biology</topic><topic>Bleomycin</topic><topic>Blocking antibodies</topic><topic>Cell adhesion & migration</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Cell Differentiation - drug effects</topic><topic>Cellular signal transduction</topic><topic>Collagen</topic><topic>Collagen Type I - metabolism</topic><topic>Cytokines</topic><topic>Dermatology</topic><topic>Disease</topic><topic>Disease Models, Animal</topic><topic>Enzyme inhibitors</topic><topic>Extracellular matrix</topic><topic>Extracellular Matrix Proteins - metabolism</topic><topic>Female</topic><topic>Fibroblasts</topic><topic>Fibrosis</topic><topic>Gene Knockout Techniques</topic><topic>Growth factors</topic><topic>Heart attacks</topic><topic>Humans</topic><topic>Immunoblotting</topic><topic>Immunohistochemistry</topic><topic>In vivo methods and tests</topic><topic>Integrin alphaV - metabolism</topic><topic>Integrins</topic><topic>Laboratories</topic><topic>Male</topic><topic>Matrix protein</topic><topic>Medical research</topic><topic>Medicine</topic><topic>Mice</topic><topic>Middle Aged</topic><topic>Myofibroblasts - drug effects</topic><topic>Myofibroblasts - metabolism</topic><topic>Myofibroblasts - pathology</topic><topic>Pathogenesis</topic><topic>Patients</topic><topic>Phosphates</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Procollagen</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-akt - metabolism</topic><topic>Rodents</topic><topic>Scleroderma</topic><topic>Scleroderma (Disease)</topic><topic>Scleroderma, Systemic - enzymology</topic><topic>Scleroderma, Systemic - pathology</topic><topic>Sclerosis</topic><topic>Signal transduction</topic><topic>Signaling</topic><topic>Skin</topic><topic>Skin - drug effects</topic><topic>Skin - pathology</topic><topic>Skin diseases</topic><topic>Transcription</topic><topic>Transduction</topic><topic>Transforming Growth Factor beta1 - pharmacology</topic><topic>Transforming growth factor-b1</topic><topic>Transforming growth factors</topic><topic>Tumor necrosis factor-TNF</topic><topic>University graduates</topic><topic>Up-Regulation - drug effects</topic><topic>Wound healing</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yang, Lingli</creatorcontrib><creatorcontrib>Serada, Satoshi</creatorcontrib><creatorcontrib>Fujimoto, Minoru</creatorcontrib><creatorcontrib>Terao, Mika</creatorcontrib><creatorcontrib>Kotobuki, Yorihisa</creatorcontrib><creatorcontrib>Kitaba, Shun</creatorcontrib><creatorcontrib>Matsui, Saki</creatorcontrib><creatorcontrib>Kudo, Akira</creatorcontrib><creatorcontrib>Naka, Tetsuji</creatorcontrib><creatorcontrib>Murota, Hiroyuki</creatorcontrib><creatorcontrib>Katayama, Ichiro</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Proquest Nursing & Allied Health Source</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>Advanced Technologies & Aerospace Collection</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>ProQuest Materials Science Collection</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yang, Lingli</au><au>Serada, Satoshi</au><au>Fujimoto, Minoru</au><au>Terao, Mika</au><au>Kotobuki, Yorihisa</au><au>Kitaba, Shun</au><au>Matsui, Saki</au><au>Kudo, Akira</au><au>Naka, Tetsuji</au><au>Murota, Hiroyuki</au><au>Katayama, Ichiro</au><au>Rossini, Alessandra</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-07-24</date><risdate>2012</risdate><volume>7</volume><issue>7</issue><spage>e41994</spage><pages>e41994-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Periostin, a novel matricellular protein, is recently reported to play a crucial role in tissue remodeling and is highly expressed under fibrotic conditions. This study was undertaken to assess the role of periostin in scleroderma.
Using skin from patients and healthy donors, the expression of periostin was assessed by immunohistochemistry and immunoblotting analyses. Furthermore, we investigated periostin(-/-) (PN(-/-)) and wild-type (WT) mice to elucidate the role of periostin in scleroderma. To induce murine cutaneous sclerosis, mice were subcutaneously injected with bleomycin, while untreated control groups were injected with phosphate-buffered saline. Bleomycin-induced fibrotic changes were compared in PN(-/-) and WT mice by histological analysis as well as by measurements of profibrotic cytokine and extracellular matrix protein expression levels in vivo and in vitro. To determine the downstream pathway involved in periostin signaling, receptor neutralizing antibody and signal transduction inhibitors were used in vitro.
Elevated expression of periostin was observed in the lesional skin of patients with scleroderma compared with healthy donors. Although WT mice showed marked cutaneous sclerosis with increased expression of periostin and increased numbers of myofibroblasts after bleomycin treatment, PN(-/-) mice showed resistance to these changes. In vitro, dermal fibroblasts from PN(-/-) mice showed reduced transcript expression of alpha smooth actin and procollagen type-I alpha 1 (Col1α1) induced by transforming growth factor beta 1 (TGFβ1). Furthermore, recombinant mouse periostin directly induced Col1α1 expression in vitro, and this effect was inhibited by blocking the αv integrin-mediated PI3K/Akt signaling either with anti-αv functional blocking antibody or with the PI3K/Akt kinase inhibitor LY294002.
Periostin plays an essential role in the pathogenesis of Bleomycin-induced scleroderma in mice. Periostin may represent a potential therapeutic target for human scleroderma.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22911870</pmid><doi>10.1371/journal.pone.0041994</doi><tpages>e41994</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2012-07, Vol.7 (7), p.e41994 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1327116329 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 1-Phosphatidylinositol 3-kinase Actin Adult Aged AKT protein Analysis Animals Antibodies Arthritis Asthma Biology Bleomycin Blocking antibodies Cell adhesion & migration Cell Adhesion Molecules - metabolism Cell Differentiation - drug effects Cellular signal transduction Collagen Collagen Type I - metabolism Cytokines Dermatology Disease Disease Models, Animal Enzyme inhibitors Extracellular matrix Extracellular Matrix Proteins - metabolism Female Fibroblasts Fibrosis Gene Knockout Techniques Growth factors Heart attacks Humans Immunoblotting Immunohistochemistry In vivo methods and tests Integrin alphaV - metabolism Integrins Laboratories Male Matrix protein Medical research Medicine Mice Middle Aged Myofibroblasts - drug effects Myofibroblasts - metabolism Myofibroblasts - pathology Pathogenesis Patients Phosphates Phosphatidylinositol 3-Kinases - metabolism Procollagen Proteins Proto-Oncogene Proteins c-akt - metabolism Rodents Scleroderma Scleroderma (Disease) Scleroderma, Systemic - enzymology Scleroderma, Systemic - pathology Sclerosis Signal transduction Signaling Skin Skin - drug effects Skin - pathology Skin diseases Transcription Transduction Transforming Growth Factor beta1 - pharmacology Transforming growth factor-b1 Transforming growth factors Tumor necrosis factor-TNF University graduates Up-Regulation - drug effects Wound healing Young Adult |
| title | Periostin facilitates skin sclerosis via PI3K/Akt dependent mechanism in a mouse model of scleroderma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-29T22%3A16%3A15IST&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=Periostin%20facilitates%20skin%20sclerosis%20via%20PI3K/Akt%20dependent%20mechanism%20in%20a%20mouse%20model%20of%20scleroderma&rft.jtitle=PloS%20one&rft.au=Yang,%20Lingli&rft.date=2012-07-24&rft.volume=7&rft.issue=7&rft.spage=e41994&rft.pages=e41994-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0041994&rft_dat=%3Cgale_plos_%3EA477045873%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=1327116329&rft_id=info:pmid/22911870&rft_galeid=A477045873&rft_doaj_id=oai_doaj_org_article_82f7587fad8043158cfb181170e30bac&rfr_iscdi=true |