{"title":"在小鼠模型中,瞬时受体电位香草素4通过调节角质形成细胞和成纤维细胞的迁移以及成纤维细胞中胶原的产生来促进皮肤伤口愈合。","authors":"Bayarmaa Taivanbat , Sahori Yamazaki , Bolor Nasanbat , Akihiko Uchiyama , Syahla Nisaa Amalia , Munkhjargal Nasan-Ochir , Yuta Inoue , Mai Ishikawa , Keiji Kosaka , Akiko Sekiguchi , Sachiko Ogino , Yoko Yokoyama , Ryoko Torii , Mari Hosoi , Koji Shibasaki , Sei-ichiro Motegi","doi":"10.1016/j.jdermsci.2023.10.002","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.</p></div><div><h3>Objective</h3><p>To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.</p></div><div><h3>Methods</h3><p>Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.</p></div><div><h3>Results</h3><p><span>TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. </span><em>In vitro</em><span><span>, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in </span>keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.</span></p></div><div><h3>Conclusion</h3><p>TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.</p></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"112 2","pages":"Pages 54-62"},"PeriodicalIF":4.6000,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model\",\"authors\":\"Bayarmaa Taivanbat , Sahori Yamazaki , Bolor Nasanbat , Akihiko Uchiyama , Syahla Nisaa Amalia , Munkhjargal Nasan-Ochir , Yuta Inoue , Mai Ishikawa , Keiji Kosaka , Akiko Sekiguchi , Sachiko Ogino , Yoko Yokoyama , Ryoko Torii , Mari Hosoi , Koji Shibasaki , Sei-ichiro Motegi\",\"doi\":\"10.1016/j.jdermsci.2023.10.002\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.</p></div><div><h3>Objective</h3><p>To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.</p></div><div><h3>Methods</h3><p>Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.</p></div><div><h3>Results</h3><p><span>TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. </span><em>In vitro</em><span><span>, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in </span>keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.</span></p></div><div><h3>Conclusion</h3><p>TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.</p></div>\",\"PeriodicalId\":94076,\"journal\":{\"name\":\"Journal of dermatological science\",\"volume\":\"112 2\",\"pages\":\"Pages 54-62\"},\"PeriodicalIF\":4.6000,\"publicationDate\":\"2023-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of dermatological science\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0923181123002256\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dermatological science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0923181123002256","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Transient receptor potential vanilloid 4 promotes cutaneous wound healing by regulating keratinocytes and fibroblasts migration and collagen production in fibroblasts in a mouse model
Background
Transient receptor potential vanilloid 4 (TRPV4), a cation ion channel, is expressed in different cells, and it regulates the development of different diseases. We recently found a high TRPV4 expression in the wounded skin area. However, the role of TRPV4 in cutaneous wound healing is unknown.
Objective
To investigate the role of TRPV4 in cutaneous wound healing in a mouse model.
Methods
Skin wound healing experiment and histopathological studies were performed between WT and TRPV4 KO mice. The effect of TRPV4 antagonist and agonist on cell migration, proliferation, and differentiation were examined in vitro.
Results
TRPV4 expression was enhanced in wounded area in the skin. TRPV4 KO mice had impaired cutaneous wound healing compared with the WT mice. Further, they had significantly suppressed re-epithelialization and formation of granulation tissue, amount of collagen deposition, and number of α-SMA-positive myofibroblasts in skin wounds. qPCR revealed that the KO mice had decreased mRNA expression of COL1A1 and ACTA2 in skin wounds. In vitro, treatment with selective TRPV4 antagonist suppressed migrating capacity, scratch stimulation enhanced the expression of phospho-ERK in keratinocytes, and TGF-β stimulation enhanced the mRNA expression of COL1A1 and ACTA2 in fibroblasts. Selective TRPV4 agonist suppressed cell migration in keratinocytes, and did not enhance proliferation and migration, but promoted differentiation in fibroblasts.
Conclusion
TRPV4 mediates keratinocytes and fibroblasts migration and increases collagen deposition in the wound area, thereby promoting cutaneous wound healing.