Hui Song Cui, You Ra Lee, Yu Mi Ro, So Young Joo, Yoon Soo Cho, June-Bum Kim, Dong Hyun Kim, Cheong Hoon Seo
{"title":"下调CPEB1和CPEB4通过调节TAK1和SMAD信号抑制疤痕形成。","authors":"Hui Song Cui, You Ra Lee, Yu Mi Ro, So Young Joo, Yoon Soo Cho, June-Bum Kim, Dong Hyun Kim, Cheong Hoon Seo","doi":"10.5021/ad.22.210","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study.</p><p><strong>Objective: </strong>This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing.</p><p><strong>Methods: </strong>CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively.</p><p><strong>Results: </strong>Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased.</p><p><strong>Conclusion: </strong>CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.</p>","PeriodicalId":8233,"journal":{"name":"Annals of Dermatology","volume":"35 4","pages":"293-302"},"PeriodicalIF":1.5000,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/2b/ad-35-293.PMC10407338.pdf","citationCount":"0","resultStr":"{\"title\":\"Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.\",\"authors\":\"Hui Song Cui, You Ra Lee, Yu Mi Ro, So Young Joo, Yoon Soo Cho, June-Bum Kim, Dong Hyun Kim, Cheong Hoon Seo\",\"doi\":\"10.5021/ad.22.210\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study.</p><p><strong>Objective: </strong>This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing.</p><p><strong>Methods: </strong>CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively.</p><p><strong>Results: </strong>Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased.</p><p><strong>Conclusion: </strong>CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.</p>\",\"PeriodicalId\":8233,\"journal\":{\"name\":\"Annals of Dermatology\",\"volume\":\"35 4\",\"pages\":\"293-302\"},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2023-08-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/12/2b/ad-35-293.PMC10407338.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annals of Dermatology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.5021/ad.22.210\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"DERMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annals of Dermatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.5021/ad.22.210","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"DERMATOLOGY","Score":null,"Total":0}
Knockdown of CPEB1 and CPEB4 Inhibits Scar Formation via Modulation of TAK1 and SMAD Signaling.
Background: Cytoplasmic polyadenylation element binding (CPEB) proteins are sequence-specific RNA-binding proteins that control translation via cytoplasmic polyadenylation. We previously reported that CPEB1 or CPEB4 knockdown suppresses TAK1 and SMAD signaling in an in vitro study.
Objective: This study aimed to investigate whether suppression of CPEB1 or CPEB4 expression inhibits scar formation in a mice model of acute dermal wound healing.
Methods: CPEB1 and CPEB4 expression levels were suppressed by siRNA treatment. Skin wounds were created by pressure-induced ulcers in mice. Images of the wound healing were obtained using a digital camera and contraction was measured by ImageJ. mRNA and protein expression was analyzed using quantitative real time polymerase chain reaction and western blotting, respectively.
Results: Wound contraction was significantly decreased by pre-treatment with CPEB1 or CPEB4 siRNA compared to the control. Suppression of CPEB1 or CPEB4 expression decreased TAK1 signaling by reducing the levels of TLR4 and TNF-α, phosphorylated TAK1, p38, ERK, JNK, and NF-κB-p65. Decreased levels of phosphorylated SMAD2 and SMAD3 indicated a reduction in SMAD signaling as well. Consequently, the expression of α-SMA, fibronectin, and type I collagen decreased.
Conclusion: CPEB1 siRNA or CPEB4 siRNA inhibit scar formation by modulating the TAK1 and SMAD signaling pathways. Our study highlights CPEB1 and CPEB4 as potential therapeutic targets for the treatment of scar formation.
期刊介绍：
Annals of Dermatology (Ann Dermatol) is the official peer-reviewed publication of the Korean Dermatological Association and the Korean Society for Investigative Dermatology. Since 1989, Ann Dermatol has contributed as a platform for communicating the latest research outcome and recent trend of dermatology in Korea and all over the world.
Ann Dermatol seeks for ameliorated understanding of skin and skin-related disease for clinicians and researchers. Ann Dermatol deals with diverse skin-related topics from laboratory investigations to clinical outcomes and invites review articles, original articles, case reports, brief reports and items of correspondence. Ann Dermatol is interested in contributions from all countries in which good and advanced research is carried out. Ann Dermatol willingly recruits well-organized and significant manuscripts with proper scope throughout the world.
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