TNF-α Induces Mitophagy in Rheumatoid Arthritis Synovial Fibroblasts, and Mitophagy Inhibition Alleviates Synovitis in Collagen Antibody-Induced Arthritis

被引：24
作者：
Nam, Ji-Hee [1 ]
Lee, Jun-Ho [2 ]
Choi, Hyun-Ji [1 ]
Choi, So-Yeon [2 ]
Noh, Kyung-Eun [1 ]
Jung, Nam-Chul [2 ]
Song, Jie-Young [3 ]
Choi, Jinjung [4 ]
Seo, Han Geuk [5 ]
Jung, Sang Youn [4 ]
Lim, Dae-Seog [1 ]
机构：
[1] CHA Univ, Dept Biotechnol, 335 Pangyo Ro, Seongnam 13488, South Korea
[2] Pharos Vaccine Inc, 14 Galmachiro,288 Bun Gil, Seongnam 13201, South Korea
[3] Korea Inst Radiol & Med Sci, Dept Radiat Canc Sci, 75 Nowon Ro, Seoul 01812, South Korea
[4] CHA Univ, Sch Med, CHA Bundang Med Ctr, Dept Internal Med,Div Rheumatol, Seongnam 13496, South Korea
[5] Konkuk Univ, Sanghuh Coll Life Sci, Dept Food Sci & Biotechnol Anim Prod, 120 Neungdong Ro, Seoul 05029, South Korea
来源：
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 10期
基金：
新加坡国家研究基金会;
关键词：
mitophagy; PINK1; rheumatoid arthritis; synovial fibroblast; TNF-alpha; MECHANISMS; PARKIN; PINK1; MITOCHONDRIA; RECRUITMENT; DISEASE; ROLES;
D O I：
10.3390/ijms23105650
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Mitophagy is a selective form of autophagy that removes damaged mitochondria. Increasing evidence indicates that dysregulated mitophagy is implicated in numerous autoimmune diseases, but the role of mitophagy in rheumatoid arthritis (RA) has not yet been reported. The aim of the present study was to determine the roles of mitophagy in patient-derived RA synovial fibroblasts (RASFs) and in the collagen antibody-induced arthritis mouse model. We measured the mitophagy marker PTEN-induced putative kinase 1 (PINK1) in RASFs treated with tumor necrosis factor-alpha (TNF-alpha) using Western blotting and immunofluorescence. Arthritis was induced in PINK1(-/-) mice by intraperitoneal injection of an anti-type II collagen antibody cocktail and lipopolysaccharide. RA severity was assessed by histopathology. PINK1 expression and damaged mitochondria increased in TNF-alpha treated RASFs via increased intracellular levels of reactive oxygen species. PINK1 knockdown RASFs decreased cellular migration and invasion functions. In addition, PINK1(-/-) mice with arthritis exhibited markedly reduced swelling and inflammation relative to wild-type mice with arthritis. Taken together, these findings suggest that regulation of PINK1 expression in RA could represent a potential therapeutic and diagnostic target for RA.
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页数：11
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共 27 条
[1]   Mutations in PTEN-induced putative kinase 1 associated with recessive parkinsonism have differential effects on protein stability [J].
Beilina, A ;
Van Der Brug, M ;
Ahmad, R ;
Kesavapanyt, S ;
Miller, DW ;
Petsko, GA ;
Cookson, MR .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (16) :5703-5708
[2]   TNF and ROS Crosstal in Inflammation [J].
Blaser, Heiko ;
Dostert, Catherine ;
Mak, Tak W. ;
Brenner, Dirk .
TRENDS IN CELL BIOLOGY, 2016, 26 (04) :249-261
[3]   PINK1 deficiency impairs adult neurogenesis of dopaminergic neurons [J].
Brown, Sarah J. ;
Boussaad, Ibrahim ;
Jarazo, Javier ;
Fitzgerald, Julia C. ;
Antony, Paul ;
Keatinge, Marcus ;
Blechman, Janna ;
Schwamborn, Jens C. ;
Krueger, Rejko ;
Placzek, Marysia ;
Bandmann, Oliver .
SCIENTIFIC REPORTS, 2021, 11 (01)
[4]   PINK1 deficiency impairs mitochondrial homeostasis and promotes lung fibrosis [J].
Bueno, Marta ;
Lai, Yen-Chun ;
Romero, Yair ;
Brands, Judith ;
Croix, Claudette M. St. ;
Kamga, Christelle ;
Corey, Catherine ;
Herazo-Maya, Jose D. ;
Sembrat, John ;
Lee, Janet S. ;
Duncan, Steve R. ;
Rojas, Mauricio ;
Shiva, Sruti ;
Chu, Charleen T. ;
Mora, Ana L. .
JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (02) :521-538
[5]   Rosiglitazone-mediated dendritic cells ameliorate collagen-induced arthritis in mice [J].
Byun, Sei-Hee ;
Lee, Jun-Ho ;
Jung, Nam-Chul ;
Choi, Hyun-Ji ;
Song, Jie-Young ;
Seo, Han Geuk ;
Choi, Jinjung ;
Jung, Sang Youn ;
Kang, Sangjin ;
Choi, Yong-Soo ;
Chung, Ji Hyung ;
Lim, Dae-Seog .
BIOCHEMICAL PHARMACOLOGY, 2016, 115 :85-93
[6]   Mechanisms of disease: Cytokine pathways and joint inflammation in rheumatoid arthritis. [J].
Choy, EHS ;
Panayi, GS .
NEW ENGLAND JOURNAL OF MEDICINE, 2001, 344 (12) :907-916
[7]   TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts [J].
Connor, Alison M. ;
Mahomed, Nizar ;
Gandhi, Rajiv ;
Keystone, Edward C. ;
Berger, Stuart A. .
ARTHRITIS RESEARCH & THERAPY, 2012, 14 (02)
[8]   Mitophagy: mechanisms, pathophysiological roles, and analysis [J].
Ding, Wen-Xing ;
Yin, Xiao-Ming .
BIOLOGICAL CHEMISTRY, 2012, 393 (07) :547-564
[9]   Innate immunity drives pathogenesis of rheumatoid arthritis [J].
Edilova, Maria, I ;
Akram, Ali ;
Abdul-Sater, Ali A. .
BIOMEDICAL JOURNAL, 2021, 44 (02) :172-182
[10]   Mitophagy in Parkinson's Disease: Pathogenic and Therapeutic Implications [J].
Gao, Fei ;
Yang, Jia ;
Wang, Dongdong ;
Li, Chao ;
Fu, Yi ;
Wang, Huaishan ;
He, Wei ;
Zhang, Jianmin .
FRONTIERS IN NEUROLOGY, 2017, 8
123