Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast-like synoviocytes by regulating the Nrf2/HO-1 pathway

Yanqiu Sun; Jian Liu; Jianting Wen; Dan Huang; Qin Zhou; Xianheng Zhang; Xiang Ding; Xiaolu Chen

doi:10.1002/iid3.663

Overexpression of long noncoding RNA LINC00638 inhibits inflammation and oxidative stress in rheumatoid arthritis fibroblast-like synoviocytes by regulating the Nrf2/HO-1 pathway

Immun Inflamm Dis. 2022 Jul;10(7):e663. doi: 10.1002/iid3.663.

Authors

Yanqiu Sun^{1

2}, Jian Liu^{2

3}, Jianting Wen^{1

2}, Dan Huang^{2

3}, Qin Zhou^{1

2}, Xianheng Zhang^{1

2}, Xiang Ding^{1

2}, Xiaolu Chen^{1

2}

Affiliations

¹ Graduate School, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.
² Department of Rheumatology, The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.
³ Institute of Rheumatology, Anhui University of Traditional Chinese Medicine, Hefei, Anhui, China.

Abstract

Background: Abnormal expression of long noncoding RNAs (lncRNAs) is involved in several autoimmune diseases including rheumatoid arthritis (RA). In this study, we intended to explore the expression of lncRNA LINC00638 in RA and its potential mechanism of action related to inflammation and oxidative stress.

Methods: The level of LINC00638 in the peripheral blood mononuclear cells (PBMCs) obtained from 45 RA patients and 30 normal controls was analyzed and its correlation with clinical indicators was investigated. In vitro, we used tumor necrosis factor-α to stimulate fibroblast-like synoviocytes (FLS) of RA patients for cell based experiments. Subsequently, the overexpressed plasmid and small interfering RNA of LINC00638 were designed. Furthermore, we further analyzed the potential effects of LINC00638 on the proliferation and migration of RA-FLS and the nuclear factor erythrocyte derived 2 related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway.

Results: LINC00638 expression was found to be significantly decreased in PBMCs of RA patients, and it was negatively correlated with erythrocyte sedimentation rate, interleukin (IL)-17, reactive oxygen species (ROS), and disease activity scores for 28 joints (DAS28). Overexpression of LINC00638 activated the Nrf2/HO-1 pathway, markedly decreased the expressions of IL-6, IL-17, IL-23, ROS, as well as malondialdehyde, increased the total antioxidant capacity, and attenuated the proliferation and migration of RA-FLS, while silencing of LINC00638 reversed these manifestations.

Conclusions: LINC00638 was found to be expressed at low levels in RA patients and was associated with immune inflammation, oxidative stress, and disease activity. Overexpression of LINC00638 can reduce the proliferation as well as migration of RA-FLS, and activate the Nrf2/HO-1 pathway to inhibit the inflammation and oxidative stress.

Keywords: LINC00638; inflammation; oxidative stress; reactive oxygen species; rheumatoid arthritis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Arthritis, Rheumatoid* / genetics
Arthritis, Rheumatoid* / metabolism
Fibroblasts / metabolism
Fibroblasts / pathology
Heme Oxygenase-1 / genetics
Heme Oxygenase-1 / metabolism
Heme Oxygenase-1 / pharmacology
Humans
Inflammation / pathology
Leukocytes, Mononuclear / metabolism
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism
NF-E2-Related Factor 2 / pharmacology
Oxidative Stress / genetics
RNA, Long Noncoding* / genetics
RNA, Long Noncoding* / metabolism
RNA, Long Noncoding* / pharmacology
Reactive Oxygen Species / metabolism
Synoviocytes* / metabolism
Synoviocytes* / pathology

Substances

NF-E2-Related Factor 2
RNA, Long Noncoding
Reactive Oxygen Species
Heme Oxygenase-1