Pub Date : 2024-09-16DOI: 10.1016/j.jid.2024.08.020
Yuta Norimatsu,Takemichi Fukasawa,Yoshinori Kabeya,Satoshi Toyama,Kazuki M Matsuda,Ai Kuzumi,Asako Yoshizaki-Ogawa,Haruka Ichimura,Sho Yonezawa,Hiroki Nakano,Shinichi Sato,Ayumi Yoshizaki
{"title":"The number of nail fold capillaries and nail fold bleedings reflects the clinical manifestations of systemic sclerosis.","authors":"Yuta Norimatsu,Takemichi Fukasawa,Yoshinori Kabeya,Satoshi Toyama,Kazuki M Matsuda,Ai Kuzumi,Asako Yoshizaki-Ogawa,Haruka Ichimura,Sho Yonezawa,Hiroki Nakano,Shinichi Sato,Ayumi Yoshizaki","doi":"10.1016/j.jid.2024.08.020","DOIUrl":"https://doi.org/10.1016/j.jid.2024.08.020","url":null,"abstract":"","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"10 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Reduced fibroblast activity is a critical factor in the progression of diabetic ulcers. CD248, a transmembrane glycoprotein prominently expressed in activated fibroblasts, plays a pivotal role in wound healing. However, the role of CD248 in diabetic wound healing and the CD248 regulatory pathway remains largely unexplored. Our study shows that CD248 expression is significantly reduced in skin wounds from both diabetic patients and mice. Single-cell transcriptome data analyses reveal a marked reduction of CD248-enriched secretory-reticular fibroblasts in diabetic wounds. We identify insulin-like growth factor-1 (IGF-1) as a key regulator of CD248 expression through the Akt/mTOR signaling pathway and the Sp1 transcription factor. Overexpression of CD248 enhances fibroblast motility, elucidating the underrepresentation of CD248-enriched fibroblasts in diabetic wounds. Immunohistochemical staining of diabetic wound samples further confirm low SP1 expression and fewer CD248-positive secretory-reticular fibroblasts. Further investigation reveals that elevated tumor necrosis factor α (TNFα) levels in diabetic environment promotes IGF-1 resistance, and inhibiting IGF-1-induced CD248 expression. In summary, our findings underscore the critical role of the IGF1-SP1-CD248 axis in activating reticular fibroblasts during wound-healing processes. Targeting this axis in fibroblasts could help develop a therapeutic regimen for diabetic ulcers.
{"title":"Deciphering the Dysregulating IGF-1-SP1-CD248 Pathway in Fibroblast Functionality during Diabetic Wound Healing.","authors":"Ya-Chu Ku,Yao-Chou Lee,Yi-Kai Hong,Yung-Ling Lo,Cheng-Hsiang Kuo,Kuan-Chieh Wang,Chao-Kai Hsu,Chien-Hung Yu,Shu-Wha Lin,Hua-Lin Wu","doi":"10.1016/j.jid.2024.07.035","DOIUrl":"https://doi.org/10.1016/j.jid.2024.07.035","url":null,"abstract":"Reduced fibroblast activity is a critical factor in the progression of diabetic ulcers. CD248, a transmembrane glycoprotein prominently expressed in activated fibroblasts, plays a pivotal role in wound healing. However, the role of CD248 in diabetic wound healing and the CD248 regulatory pathway remains largely unexplored. Our study shows that CD248 expression is significantly reduced in skin wounds from both diabetic patients and mice. Single-cell transcriptome data analyses reveal a marked reduction of CD248-enriched secretory-reticular fibroblasts in diabetic wounds. We identify insulin-like growth factor-1 (IGF-1) as a key regulator of CD248 expression through the Akt/mTOR signaling pathway and the Sp1 transcription factor. Overexpression of CD248 enhances fibroblast motility, elucidating the underrepresentation of CD248-enriched fibroblasts in diabetic wounds. Immunohistochemical staining of diabetic wound samples further confirm low SP1 expression and fewer CD248-positive secretory-reticular fibroblasts. Further investigation reveals that elevated tumor necrosis factor α (TNFα) levels in diabetic environment promotes IGF-1 resistance, and inhibiting IGF-1-induced CD248 expression. In summary, our findings underscore the critical role of the IGF1-SP1-CD248 axis in activating reticular fibroblasts during wound-healing processes. Targeting this axis in fibroblasts could help develop a therapeutic regimen for diabetic ulcers.","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"23 1","pages":""},"PeriodicalIF":6.5,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142247612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-14DOI: 10.1016/j.jid.2024.07.032
Tyler B. Cepica , Radhika Gupta , Victoria P. Werth , Benjamin F. Chong
Despite the significant disease burden of cutaneous lupus erythematosus (CLE), there have been no United States Food and Drug Administration–approved therapies for 65 years. To facilitate advancement of therapies, severity scores are needed to evaluate QOL, how patients feel, activity of disease, and organ-specific damage to assess response to therapies and disease progression. In this paper, we delineate the development process of provider- and patient-reported severity scores for CLE. Cutaneous Lupus Disease Area and Severity Index (CLASI), a provider-reported measure that distinguishes between activity and damage, has undergone rigorous validation and reliability testing for over 20 years. Its performance has been tested in clinical trials as a primary or secondary endpoint and tool to stratify patients. As an objective disease measure that captures a provider’s perspective of disease activity and damage, the CLASI inherently does not assess disease impact on patients’ QOL. Cutaneous Lupus Erythematosus Quality of Life (CLEQoL), a patient-reported measure, captures features elucidated through focus groups, including symptoms, emotions, functioning, body image, and photosensitivity. It has undergone psychometric property testing to ensure reliability and validity. Together, CLASI and CLEQoL are simple and reliable CLE-specific severity scores capturing disease activity, damage, and QOL from provider and patient perspectives.
{"title":"Severity Scores for Cutaneous Lupus Erythematosus","authors":"Tyler B. Cepica , Radhika Gupta , Victoria P. Werth , Benjamin F. Chong","doi":"10.1016/j.jid.2024.07.032","DOIUrl":"10.1016/j.jid.2024.07.032","url":null,"abstract":"<div><div>Despite the significant disease burden of cutaneous lupus erythematosus (CLE), there have been no United States Food and Drug Administration–approved therapies for 65 years. To facilitate advancement of therapies, severity scores are needed to evaluate QOL, how patients feel, activity of disease, and organ-specific damage to assess response to therapies and disease progression. In this paper, we delineate the development process of provider- and patient-reported severity scores for CLE. Cutaneous Lupus Disease Area and Severity Index (CLASI), a provider-reported measure that distinguishes between activity and damage, has undergone rigorous validation and reliability testing for over 20 years. Its performance has been tested in clinical trials as a primary or secondary endpoint and tool to stratify patients. As an objective disease measure that captures a provider’s perspective of disease activity and damage, the CLASI inherently does not assess disease impact on patients’ QOL. Cutaneous Lupus Erythematosus Quality of Life (CLEQoL), a patient-reported measure, captures features elucidated through focus groups, including symptoms, emotions, functioning, body image, and photosensitivity. It has undergone psychometric property testing to ensure reliability and validity. Together, CLASI and CLEQoL are simple and reliable CLE-specific severity scores capturing disease activity, damage, and QOL from provider and patient perspectives.</div></div>","PeriodicalId":16311,"journal":{"name":"Journal of Investigative Dermatology","volume":"144 11","pages":"Pages 2354-2363"},"PeriodicalIF":5.7,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142305325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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