Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis
Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis....
Gespeichert in:
| Veröffentlicht in: | The Journal of clinical investigation 2021-01, Vol.131 (1), p.1-13 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 13 |
|---|---|
| container_issue | 1 |
| container_start_page | 1 |
| container_title | The Journal of clinical investigation |
| container_volume | 131 |
| creator | Chen, Hung-Lin Lo, Chia-Hui Huang, Chi-Chun Lu, Meng-Ping Hu, Po-Yuan Chen, Chang-Shan Chueh, Di-Yen Chen, Peilin Lin, Teng-Nan Lo, Yuan-Hsin Hsiao, Yu-Ping Hsu, Daniel K Liu, Fu-Tong |
| description | Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis. |
| doi_str_mv | 10.1172/JCI130740 |
| format | Article |
| fullrecord | <record><control><sourceid>gale_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7773376</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><galeid>A647748463</galeid><sourcerecordid>A647748463</sourcerecordid><originalsourceid>FETCH-LOGICAL-c607t-6677ef0e89cd4214eaa48ff88b4a43509402b62ed91832b5787947c0e3d2a2433</originalsourceid><addsrcrecordid>eNqNkk2LFDEQhhtR3HH14B-QgCDrodd8dSd9EYZhXUcGFvy6hnS6uie7mWS2060O-ONN4zruyBwkhxSVp94U9VaWPSf4nBBB33xYLAnDguMH2YwUhcwlZfJhNsOYkrwSTJ5kT2K8xphwXvDH2QljuCg4qWbZz0vtwAzW5wI14bvvoRudHmzwyHrkIKZIO3QDfUr6YHYDRGSCH3pbj1M8BAR-rb2BBi1XORFzFG2XaqzvkPYNijdJaKuHdXCh202q2xh6q6ONT7NHrXYRnt3dp9mXdxefF-_z1dXlcjFf5abEYsjLUghoMcjKNJwSDlpz2bZS1lxzVuCKY1qXFJqKSEbrQkhRcWEwsIZqyhk7zd7-1t2O9QYaA6l97dS2txvd71TQVh2-eLtWXfimhBCMiTIJnN0J9OF2hDiojY0GnNMewhgV5QWRRUkITejLf9DrMPZpHhMlSlnKSuK_VJfGr6xvQ_rXTKJqXnIhuOTl1Hd-hOrAJzdc8NDalD7gz4_w6TSwseZoweuDgslY-DF0eoxRLT99_H_26ush--oeuwbthnUMbpz2Kh4VNX2IsYd2bwrBatpttd_txL647-Ke_LPM7BeIePCX</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2476868980</pqid></control><display><type>article</type><title>Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis</title><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Alma/SFX Local Collection</source><creator>Chen, Hung-Lin ; Lo, Chia-Hui ; Huang, Chi-Chun ; Lu, Meng-Ping ; Hu, Po-Yuan ; Chen, Chang-Shan ; Chueh, Di-Yen ; Chen, Peilin ; Lin, Teng-Nan ; Lo, Yuan-Hsin ; Hsiao, Yu-Ping ; Hsu, Daniel K ; Liu, Fu-Tong</creator><creatorcontrib>Chen, Hung-Lin ; Lo, Chia-Hui ; Huang, Chi-Chun ; Lu, Meng-Ping ; Hu, Po-Yuan ; Chen, Chang-Shan ; Chueh, Di-Yen ; Chen, Peilin ; Lin, Teng-Nan ; Lo, Yuan-Hsin ; Hsiao, Yu-Ping ; Hsu, Daniel K ; Liu, Fu-Tong</creatorcontrib><description>Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.</description><identifier>ISSN: 0021-9738</identifier><identifier>EISSN: 1558-8238</identifier><identifier>DOI: 10.1172/JCI130740</identifier><identifier>PMID: 33055419</identifier><language>eng</language><publisher>United States: American Society for Clinical Investigation</publisher><subject>Biomedical research ; Care and treatment ; Cellular signal transduction ; Chemokines ; Cytokines ; Development and progression ; Disease ; Fluvastatin ; Genetic aspects ; Genetic regulation ; Health aspects ; Homeostasis ; Hyperplasia ; Inflammation ; Interleukin 23 ; Interleukin 6 ; Interleukin 8 ; Keratinocytes ; Kinases ; Lactose ; Lectins ; Metabolic pathways ; Metabolic syndrome ; MicroRNAs ; miRNA ; Neutrophils ; Pathogenesis ; Protein expression ; Proteins ; Psoriasis ; Skin diseases ; Skin lesions ; Statins ; Tumor necrosis factor-α</subject><ispartof>The Journal of clinical investigation, 2021-01, Vol.131 (1), p.1-13</ispartof><rights>COPYRIGHT 2021 American Society for Clinical Investigation</rights><rights>Copyright American Society for Clinical Investigation Jan 2021</rights><rights>2021 American Society for Clinical Investigation 2021 American Society for Clinical Investigation</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c607t-6677ef0e89cd4214eaa48ff88b4a43509402b62ed91832b5787947c0e3d2a2433</citedby><cites>FETCH-LOGICAL-c607t-6677ef0e89cd4214eaa48ff88b4a43509402b62ed91832b5787947c0e3d2a2433</cites><orcidid>0000-0003-4154-0487 ; 0000-0002-8482-4108 ; 0000-0002-3727-9696 ; 0000-0002-3339-9391 ; 0000-0003-1459-1553 ; 0000-0002-4009-0798 ; 0000-0001-7900-3391 ; 0000-0003-4989-7261</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773376/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7773376/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33055419$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chen, Hung-Lin</creatorcontrib><creatorcontrib>Lo, Chia-Hui</creatorcontrib><creatorcontrib>Huang, Chi-Chun</creatorcontrib><creatorcontrib>Lu, Meng-Ping</creatorcontrib><creatorcontrib>Hu, Po-Yuan</creatorcontrib><creatorcontrib>Chen, Chang-Shan</creatorcontrib><creatorcontrib>Chueh, Di-Yen</creatorcontrib><creatorcontrib>Chen, Peilin</creatorcontrib><creatorcontrib>Lin, Teng-Nan</creatorcontrib><creatorcontrib>Lo, Yuan-Hsin</creatorcontrib><creatorcontrib>Hsiao, Yu-Ping</creatorcontrib><creatorcontrib>Hsu, Daniel K</creatorcontrib><creatorcontrib>Liu, Fu-Tong</creatorcontrib><title>Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis</title><title>The Journal of clinical investigation</title><addtitle>J Clin Invest</addtitle><description>Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.</description><subject>Biomedical research</subject><subject>Care and treatment</subject><subject>Cellular signal transduction</subject><subject>Chemokines</subject><subject>Cytokines</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Fluvastatin</subject><subject>Genetic aspects</subject><subject>Genetic regulation</subject><subject>Health aspects</subject><subject>Homeostasis</subject><subject>Hyperplasia</subject><subject>Inflammation</subject><subject>Interleukin 23</subject><subject>Interleukin 6</subject><subject>Interleukin 8</subject><subject>Keratinocytes</subject><subject>Kinases</subject><subject>Lactose</subject><subject>Lectins</subject><subject>Metabolic pathways</subject><subject>Metabolic syndrome</subject><subject>MicroRNAs</subject><subject>miRNA</subject><subject>Neutrophils</subject><subject>Pathogenesis</subject><subject>Protein expression</subject><subject>Proteins</subject><subject>Psoriasis</subject><subject>Skin diseases</subject><subject>Skin lesions</subject><subject>Statins</subject><subject>Tumor necrosis factor-α</subject><issn>0021-9738</issn><issn>1558-8238</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqNkk2LFDEQhhtR3HH14B-QgCDrodd8dSd9EYZhXUcGFvy6hnS6uie7mWS2060O-ONN4zruyBwkhxSVp94U9VaWPSf4nBBB33xYLAnDguMH2YwUhcwlZfJhNsOYkrwSTJ5kT2K8xphwXvDH2QljuCg4qWbZz0vtwAzW5wI14bvvoRudHmzwyHrkIKZIO3QDfUr6YHYDRGSCH3pbj1M8BAR-rb2BBi1XORFzFG2XaqzvkPYNijdJaKuHdXCh202q2xh6q6ONT7NHrXYRnt3dp9mXdxefF-_z1dXlcjFf5abEYsjLUghoMcjKNJwSDlpz2bZS1lxzVuCKY1qXFJqKSEbrQkhRcWEwsIZqyhk7zd7-1t2O9QYaA6l97dS2txvd71TQVh2-eLtWXfimhBCMiTIJnN0J9OF2hDiojY0GnNMewhgV5QWRRUkITejLf9DrMPZpHhMlSlnKSuK_VJfGr6xvQ_rXTKJqXnIhuOTl1Hd-hOrAJzdc8NDalD7gz4_w6TSwseZoweuDgslY-DF0eoxRLT99_H_26ush--oeuwbthnUMbpz2Kh4VNX2IsYd2bwrBatpttd_txL647-Ke_LPM7BeIePCX</recordid><startdate>20210101</startdate><enddate>20210101</enddate><creator>Chen, Hung-Lin</creator><creator>Lo, Chia-Hui</creator><creator>Huang, Chi-Chun</creator><creator>Lu, Meng-Ping</creator><creator>Hu, Po-Yuan</creator><creator>Chen, Chang-Shan</creator><creator>Chueh, Di-Yen</creator><creator>Chen, Peilin</creator><creator>Lin, Teng-Nan</creator><creator>Lo, Yuan-Hsin</creator><creator>Hsiao, Yu-Ping</creator><creator>Hsu, Daniel K</creator><creator>Liu, Fu-Tong</creator><general>American Society for Clinical Investigation</general><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BEC</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB0</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>S0X</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-4154-0487</orcidid><orcidid>https://orcid.org/0000-0002-8482-4108</orcidid><orcidid>https://orcid.org/0000-0002-3727-9696</orcidid><orcidid>https://orcid.org/0000-0002-3339-9391</orcidid><orcidid>https://orcid.org/0000-0003-1459-1553</orcidid><orcidid>https://orcid.org/0000-0002-4009-0798</orcidid><orcidid>https://orcid.org/0000-0001-7900-3391</orcidid><orcidid>https://orcid.org/0000-0003-4989-7261</orcidid></search><sort><creationdate>20210101</creationdate><title>Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis</title><author>Chen, Hung-Lin ; Lo, Chia-Hui ; Huang, Chi-Chun ; Lu, Meng-Ping ; Hu, Po-Yuan ; Chen, Chang-Shan ; Chueh, Di-Yen ; Chen, Peilin ; Lin, Teng-Nan ; Lo, Yuan-Hsin ; Hsiao, Yu-Ping ; Hsu, Daniel K ; Liu, Fu-Tong</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c607t-6677ef0e89cd4214eaa48ff88b4a43509402b62ed91832b5787947c0e3d2a2433</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Biomedical research</topic><topic>Care and treatment</topic><topic>Cellular signal transduction</topic><topic>Chemokines</topic><topic>Cytokines</topic><topic>Development and progression</topic><topic>Disease</topic><topic>Fluvastatin</topic><topic>Genetic aspects</topic><topic>Genetic regulation</topic><topic>Health aspects</topic><topic>Homeostasis</topic><topic>Hyperplasia</topic><topic>Inflammation</topic><topic>Interleukin 23</topic><topic>Interleukin 6</topic><topic>Interleukin 8</topic><topic>Keratinocytes</topic><topic>Kinases</topic><topic>Lactose</topic><topic>Lectins</topic><topic>Metabolic pathways</topic><topic>Metabolic syndrome</topic><topic>MicroRNAs</topic><topic>miRNA</topic><topic>Neutrophils</topic><topic>Pathogenesis</topic><topic>Protein expression</topic><topic>Proteins</topic><topic>Psoriasis</topic><topic>Skin diseases</topic><topic>Skin lesions</topic><topic>Statins</topic><topic>Tumor necrosis factor-α</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Chen, Hung-Lin</creatorcontrib><creatorcontrib>Lo, Chia-Hui</creatorcontrib><creatorcontrib>Huang, Chi-Chun</creatorcontrib><creatorcontrib>Lu, Meng-Ping</creatorcontrib><creatorcontrib>Hu, Po-Yuan</creatorcontrib><creatorcontrib>Chen, Chang-Shan</creatorcontrib><creatorcontrib>Chueh, Di-Yen</creatorcontrib><creatorcontrib>Chen, Peilin</creatorcontrib><creatorcontrib>Lin, Teng-Nan</creatorcontrib><creatorcontrib>Lo, Yuan-Hsin</creatorcontrib><creatorcontrib>Hsiao, Yu-Ping</creatorcontrib><creatorcontrib>Hsu, Daniel K</creatorcontrib><creatorcontrib>Liu, Fu-Tong</creatorcontrib><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>ProQuest Nursing and Allied Health Source</collection><collection>ProQuest_Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>ProQuest SciTech 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>ProQuest Central (Alumni)</collection><collection>ProQuest Central</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>eLibrary</collection><collection>ProQuest Central</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Biological Sciences</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>PML(ProQuest Medical Library)</collection><collection>Biological Science Database</collection><collection>Nursing & Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>SIRS Editorial</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The Journal of clinical investigation</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chen, Hung-Lin</au><au>Lo, Chia-Hui</au><au>Huang, Chi-Chun</au><au>Lu, Meng-Ping</au><au>Hu, Po-Yuan</au><au>Chen, Chang-Shan</au><au>Chueh, Di-Yen</au><au>Chen, Peilin</au><au>Lin, Teng-Nan</au><au>Lo, Yuan-Hsin</au><au>Hsiao, Yu-Ping</au><au>Hsu, Daniel K</au><au>Liu, Fu-Tong</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis</atitle><jtitle>The Journal of clinical investigation</jtitle><addtitle>J Clin Invest</addtitle><date>2021-01-01</date><risdate>2021</risdate><volume>131</volume><issue>1</issue><spage>1</spage><epage>13</epage><pages>1-13</pages><issn>0021-9738</issn><eissn>1558-8238</eissn><abstract>Psoriasis is a chronic inflammatory skin disease characterized by inflammatory cell infiltration, as well as hyperproliferation of keratinocytes in skin lesions, and is considered a metabolic syndrome. We found that the expression of galectin-7 is reduced in skin lesions of patients with psoriasis. IL-17A and TNF-α, 2 cytokines intimately involved in the development of psoriatic lesions, suppressed galectin-7 expression in human primary keratinocytes (HEKn cells) and the immortalized human keratinocyte cell line HaCaT. A galectin-7 knockdown in these cells elevated the production of IL-6 and IL-8 and enhanced ERK signaling when the cells were stimulated with IL-17A. Galectin-7 attenuated IL-17A-induced production of inflammatory mediators by keratinocytes via the microRNA-146a/ERK pathway. Moreover, galectin-7-deficient mice showed enhanced epidermal hyperplasia and skin inflammation in response to intradermal IL-23 injection. We identified fluvastatin as an inducer of galectin-7 expression by connectivity map analysis, confirmed this effect in keratinocytes, and demonstrated that fluvastatin attenuated IL-6 and IL-8 production induced by IL-17A. Thus, we validate a role of galectin-7 in the pathogenesis of psoriasis, in both epidermal hyperplasia and keratinocyte-mediated inflammatory responses, and formulate a rationale for the use of statins in the treatment of psoriasis.</abstract><cop>United States</cop><pub>American Society for Clinical Investigation</pub><pmid>33055419</pmid><doi>10.1172/JCI130740</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0003-4154-0487</orcidid><orcidid>https://orcid.org/0000-0002-8482-4108</orcidid><orcidid>https://orcid.org/0000-0002-3727-9696</orcidid><orcidid>https://orcid.org/0000-0002-3339-9391</orcidid><orcidid>https://orcid.org/0000-0003-1459-1553</orcidid><orcidid>https://orcid.org/0000-0002-4009-0798</orcidid><orcidid>https://orcid.org/0000-0001-7900-3391</orcidid><orcidid>https://orcid.org/0000-0003-4989-7261</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0021-9738 |
| ispartof | The Journal of clinical investigation, 2021-01, Vol.131 (1), p.1-13 |
| issn | 0021-9738 1558-8238 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7773376 |
| source | EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Biomedical research Care and treatment Cellular signal transduction Chemokines Cytokines Development and progression Disease Fluvastatin Genetic aspects Genetic regulation Health aspects Homeostasis Hyperplasia Inflammation Interleukin 23 Interleukin 6 Interleukin 8 Keratinocytes Kinases Lactose Lectins Metabolic pathways Metabolic syndrome MicroRNAs miRNA Neutrophils Pathogenesis Protein expression Proteins Psoriasis Skin diseases Skin lesions Statins Tumor necrosis factor-α |
| title | Galectin-7 downregulation in lesional keratinocytes contributes to enhanced IL-17A signaling and skin pathology in psoriasis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T08%3A15%3A37IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Galectin-7%20downregulation%20in%20lesional%20keratinocytes%20contributes%20to%20enhanced%20IL-17A%20signaling%20and%20skin%20pathology%20in%20psoriasis&rft.jtitle=The%20Journal%20of%20clinical%20investigation&rft.au=Chen,%20Hung-Lin&rft.date=2021-01-01&rft.volume=131&rft.issue=1&rft.spage=1&rft.epage=13&rft.pages=1-13&rft.issn=0021-9738&rft.eissn=1558-8238&rft_id=info:doi/10.1172/JCI130740&rft_dat=%3Cgale_pubme%3EA647748463%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2476868980&rft_id=info:pmid/33055419&rft_galeid=A647748463&rfr_iscdi=true |