Ying Wu , Yiting Gong , Yiming Ma , Qiaofan Zhao , Ruyu Fu , Xiaoming Zhang , Ye Li , Xueyuan Zhi
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VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)<sub>2</sub>D<sub>3</sub> intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in <em>Timp1</em> mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)<sub>2</sub>D<sub>3</sub>. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)<sub>2</sub>D<sub>3</sub> appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)<sub>2</sub>D<sub>3</sub> tended to enhance EMT and ECM.</p></div>","PeriodicalId":16618,"journal":{"name":"Journal of Nutritional Biochemistry","volume":"134 ","pages":"Article 109733"},"PeriodicalIF":4.8000,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Effects of vitamin D status on cutaneous wound healing through modulation of EMT and ECM\",\"authors\":\"Ying Wu , Yiting Gong , Yiming Ma , Qiaofan Zhao , Ruyu Fu , Xiaoming Zhang , Ye Li , Xueyuan Zhi\",\"doi\":\"10.1016/j.jnutbio.2024.109733\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>To investigate the effects of vitamin D status on cutaneous wound healing, C57BL/6J mice were fed diets with different vitamin D levels or injected intraperitoneally with 1α,25(OH)<sub>2</sub>D<sub>3</sub>. Dorsal skin wounds were created and wound edge tissues were collected on days 4, 7, 11, and 14 postwounding. The proliferation and migration of HaCaT cells treated with shVDR or 1α,25(OH)<sub>2</sub>D<sub>3</sub> were assessed. Vitamin D deficiency (VDD) decreased wound closure and might delay inflammatory response, shown by slower inflammatory cell infiltration, decreased IL6 and TNF expression in early phase followed by an increase later. VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)<sub>2</sub>D<sub>3</sub> intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in <em>Timp1</em> mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)<sub>2</sub>D<sub>3</sub>. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)<sub>2</sub>D<sub>3</sub> appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)<sub>2</sub>D<sub>3</sub> tended to enhance EMT and ECM.</p></div>\",\"PeriodicalId\":16618,\"journal\":{\"name\":\"Journal of Nutritional Biochemistry\",\"volume\":\"134 \",\"pages\":\"Article 109733\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-08-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nutritional Biochemistry\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0955286324001621\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutritional Biochemistry","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0955286324001621","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
为了研究维生素 D 状态对皮肤伤口愈合的影响,给 C57BL/6J 小鼠喂食不同维生素 D 水平的食物或腹腔注射 1α,25(OH)2D3。小鼠背侧皮肤伤口,在伤口愈合后第4、7、11和14天收集伤口边缘组织。评估经 shVDR 或 1α,25(OH)2D3处理的 HaCaT 细胞的增殖和迁移情况。维生素 D 缺乏(VDD)会降低伤口闭合速度,并可能延迟炎症反应,表现为炎症细胞浸润速度减慢,IL6 和 TNF 表达早期减少,后期增加。维生素 DD 可能会推迟上皮-间质转化(EMT),初期表现为上皮标志物增加,间质标志物减少,后期则相反。膳食维生素 D 补充剂和 1α,25(OH)2D3干预往往会加速 EMT。在细胞外基质(ECM)方面,VDD似乎在第4天减少了胶原沉积,并在早期下调了纤连蛋白、COL3A1和MMP9的表达,随后又有所增加,同时Timp1 mRNA的表达也出现了先增后减的现象。膳食维生素 D 的干预在第 4 天促进了纤维粘连蛋白和 MMP9 的表达,然后在第 14 天下调了它们的表达。TGFb1/SMAD2/3信号似乎受VDD下调,而受1α,25(OH)2D3上调。在体外,通过 shVDR 部分抑制 VDR 往往会抑制 HaCaT 细胞的增殖和迁移、EMT 和 TGFb1/SMAD2/3 信号传导,而 1α,25(OH)2D3似乎会产生相反的效果。总之,维生素 D阻碍了皮肤伤口愈合,这可能是由于炎症反应受损、EMT延迟、ECM减少以及TGFb1/SMAD2/3途径受到抑制。维生素 D 和 1α,25(OH)2D3 有增强 EMT 和 ECM 的趋势。
Effects of vitamin D status on cutaneous wound healing through modulation of EMT and ECM
To investigate the effects of vitamin D status on cutaneous wound healing, C57BL/6J mice were fed diets with different vitamin D levels or injected intraperitoneally with 1α,25(OH)2D3. Dorsal skin wounds were created and wound edge tissues were collected on days 4, 7, 11, and 14 postwounding. The proliferation and migration of HaCaT cells treated with shVDR or 1α,25(OH)2D3 were assessed. Vitamin D deficiency (VDD) decreased wound closure and might delay inflammatory response, shown by slower inflammatory cell infiltration, decreased IL6 and TNF expression in early phase followed by an increase later. VDD might postpone epithelial-mesenchymal transition (EMT), initially characterized by higher epithelial markers and lower mesenchymal markers, followed by opposite appearance later. Dietary vitamin D supplementation and 1α,25(OH)2D3 intervention tended to accelerate EMT. Regarding extracellular matrix (ECM), VDD appeared to reduce collagen deposition on day 4 and downregulated fibronectin, COL3A1, and MMP9 expression early, followed by an increase later, together with an initial increase and subsequent decrease in Timp1 mRNA expression. Dietary vitamin D intervention promoted fibronectin and MMP9 expression on day 4 and then downregulated their expression on day 14. TGFb1/SMAD2/3 signaling seemed to be downregulated by VDD and upregulated by 1α,25(OH)2D3. In vitro, partial inhibition of VDR by shVDR tended to inhibit HaCaT cell proliferation and migration, EMT, and TGFb1/SMAD2/3 signaling, whereas 1α,25(OH)2D3 appeared to generate opposite effects. In conclusion, VDD hindered cutaneous wound healing, potentially due to impaired inflammatory response, delayed EMT, decreased ECM, and inhibited TGFb1/SMAD2/3 pathway. Vitamin D and 1α,25(OH)2D3 tended to enhance EMT and ECM.
期刊介绍:
Devoted to advancements in nutritional sciences, The Journal of Nutritional Biochemistry presents experimental nutrition research as it relates to: biochemistry, molecular biology, toxicology, or physiology.
Rigorous reviews by an international editorial board of distinguished scientists ensure publication of the most current and key research being conducted in nutrition at the cellular, animal and human level. In addition to its monthly features of critical reviews and research articles, The Journal of Nutritional Biochemistry also periodically publishes emerging issues, experimental methods, and other types of articles.