Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis

Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis

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 autoph...

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Main Authors: Weiyan Wang, Chunling Li, Zhiyi Zhang, Yue Zhang
Format: Article
Language:English
Published: Hindawi Limited 2019-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2019/6403504
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spelling doaj-422f9805be1343ee8724e199187952112020-11-24T22:11:41ZengHindawi LimitedPPAR Research1687-47571687-47652019-01-01201910.1155/2019/64035046403504Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid ArthritisWeiyan Wang0Chunling Li1Zhiyi Zhang2Yue Zhang3Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St., Nangang District, Harbin, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St., Nangang District, Harbin, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St., Nangang District, Harbin, ChinaDepartment of Rheumatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng St., Nangang District, Harbin, ChinaDysregulated 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.http://dx.doi.org/10.1155/2019/6403504
collection DOAJ
language English
format Article
sources DOAJ
author Weiyan Wang
Chunling Li
Zhiyi Zhang
Yue Zhang
spellingShingle Weiyan Wang
Chunling Li
Zhiyi Zhang
Yue Zhang
Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
PPAR Research
author_facet Weiyan Wang
Chunling Li
Zhiyi Zhang
Yue Zhang
author_sort Weiyan Wang
title Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
title_short Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
title_full Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
title_fullStr Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
title_full_unstemmed Arsenic Trioxide in Synergy with Vitamin D Rescues the Defective VDR-PPAR-γ Functional Module of Autophagy in Rheumatoid Arthritis
title_sort arsenic trioxide in synergy with vitamin d rescues the defective vdr-ppar-γ functional module of autophagy in rheumatoid arthritis
publisher Hindawi Limited
series PPAR Research
issn 1687-4757
1687-4765
publishDate 2019-01-01
description 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.
url http://dx.doi.org/10.1155/2019/6403504
work_keys_str_mv AT weiyanwang arsenictrioxideinsynergywithvitamindrescuesthedefectivevdrppargfunctionalmoduleofautophagyinrheumatoidarthritis
AT chunlingli arsenictrioxideinsynergywithvitamindrescuesthedefectivevdrppargfunctionalmoduleofautophagyinrheumatoidarthritis
AT zhiyizhang arsenictrioxideinsynergywithvitamindrescuesthedefectivevdrppargfunctionalmoduleofautophagyinrheumatoidarthritis
AT yuezhang arsenictrioxideinsynergywithvitamindrescuesthedefectivevdrppargfunctionalmoduleofautophagyinrheumatoidarthritis
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