{"title":"Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-<i>γ</i> Functional Module of Autophagy in Rheumatoid Arthritis.","authors":"Weiyan Wang, Chunling Li, Zhiyi Zhang, Yue Zhang","doi":"10.1155/2019/6403504","DOIUrl":null,"url":null,"abstract":"<p><p>Dysregulated autophagy leads to autoimmune diseases including rheumatoid arthritis (RA). Arsenic trioxide (ATO) is a single agent used for the treatment of acute promyelocytic leukemia and is highly promising for other malignancies but is also attractive for RA, although its relationship with autophagy remains to be further clarified and its application optimized. For the first time, we report a defective functional module of autophagy comprising the Vitamin D receptor (VDR), PPAR-<i>γ</i>, microtubule-associated protein 1 light-chain 3 (LC3), and p62 which appears in RA synovial fibroblasts. ATO alleviated RA symptoms by boosting effective autophagic flux through significantly downregulating p62, the inflammation and catabolism protein. Importantly, low-dose ATO synergizes with Vitamin D in RA treatment.</p>","PeriodicalId":20439,"journal":{"name":"PPAR Research","volume":"2019 ","pages":"6403504"},"PeriodicalIF":3.5000,"publicationDate":"2019-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/6403504","citationCount":"17","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"PPAR Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/2019/6403504","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2019/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 17
Abstract
Dysregulated autophagy leads to autoimmune diseases including rheumatoid arthritis (RA). Arsenic trioxide (ATO) is a single agent used for the treatment of acute promyelocytic leukemia and is highly promising for other malignancies but is also attractive for RA, although its relationship with autophagy remains to be further clarified and its application optimized. For the first time, we report a defective functional module of autophagy comprising the Vitamin D receptor (VDR), PPAR-γ, microtubule-associated protein 1 light-chain 3 (LC3), and p62 which appears in RA synovial fibroblasts. ATO alleviated RA symptoms by boosting effective autophagic flux through significantly downregulating p62, the inflammation and catabolism protein. Importantly, low-dose ATO synergizes with Vitamin D in RA treatment.
期刊介绍：
PPAR Research is a peer-reviewed, Open Access journal that publishes original research and review articles on advances in basic research focusing on mechanisms involved in the activation of peroxisome proliferator-activated receptors (PPARs), as well as their role in the regulation of cellular differentiation, development, energy homeostasis and metabolic function. The journal also welcomes preclinical and clinical trials of drugs that can modulate PPAR activity, with a view to treating chronic diseases and disorders such as dyslipidemia, diabetes, adipocyte differentiation, inflammation, cancer, lung diseases, neurodegenerative disorders, and obesity.
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