KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis

被引：10
作者：
Huang, Dan [1 ]
Tao, Liju [1 ]
Du, Xiuri [1 ]
机构：
[1] Youjiang Med Coll Nationalities, Dept Rheumatol & Immunol, Affiliated Hosp, 18 Zhongshan Second Rd, Baise 533000, Guangxi Zhuang, Peoples R China
来源：
IMMUNITY INFLAMMATION AND DISEASE | 2022年 / 10卷 / 11期
关键词：
KLF9; rheumatoid arthritis; synovial fibroblasts; TRIM33; MATRIX METALLOPROTEINASES; CELL-PROLIFERATION; SYNOVIOCYTES; CANCER; EXPRESSION; INFILTRATE; ALPHA; MOTIF;
D O I：
10.1002/iid3.696
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background: Rheumatoid arthritis (RA) can cause irreversible joint injury and serious disability. This study aimed to investigate how TRIM33 regulated by KLF9 affects the aggressive behaviors of synovial fibroblasts induced by tumor necrosis factor-alpha (TNF-alpha). Materials and Methods: TNF-alpha-induced MH7A cells were used to simulate the in vitro model of RA. TRIM33 and KLF9 expression in TNF-alpha-challenged MH7A cells and transfection efficiency were analyzed via real-time reverse transcription polymerase chain reaction together with western blot. The viability, proliferation, invasion, and migration of TNF-alpha-induced MH7A cells after transfection was respectively detected by CCK-8, EdU staining, transwell, and wound-healing assays. The expression of invasion and migration-related proteins and inflammation-related proteins was determined by western blot and the levels of inflammatory factors were detected by enzyme-linked immunosorbent assay. The combination between TRIM33 and KLF9 was substantiated through dual-luciferase reporter assay and chromatin immunoprecipitation. Results: TRIM33 and KLF9 expression in TNF-alpha-challenged MH7A cells was downregulated. TRIM33 elevation inhibited TNF-alpha-elicited proliferation, metastasis as well as inflammation of MH7A cells. Moreover, KLF9 was combined with TRIM33 and KLF9 promoted transcription of TRIM33. The inhibitory effect of TRIM33 overexpression on proliferation, invasion and migration and inflammation of MH7A cells induced by TNF-alpha was alleviated by the downregulation of KLF9. Conclusion: KLF9 positively regulates TRIM33 to suppress the abnormal MH7A cell proliferation, migration, and reduce inflammation upon exposure to TNF-alpha, which was reversed by inhibiting KLF9.
引用
收藏
页数：10
相关论文
共 35 条
[11]   HIF-2α-induced chemokines stimulate motility of fibroblast-like synoviocytes and chondrocytes into the cartilage-pannus interface in experimental rheumatoid arthritis mouse models [J].
Huh, Yun Hyun ;
Lee, Gyuseok ;
Lee, Keun-Bae ;
Koh, Jeong-Tae ;
Chun, Jang-Soo ;
Ryu, Je-Hwang .
ARTHRITIS RESEARCH & THERAPY, 2015, 17
[12]   Tripartite Motif-containing 33 (TRIM33) Protein Functions in the Poly(ADP-ribose) Polymerase (PARP)-dependent DNA Damage Response through Interaction with Amplified in Liver Cancer 1 (ALC1) Protein [J].
Kulkarni, Atul ;
Oza, Jay ;
Yao, Ming ;
Sohail, Honeah ;
Ginjala, Vasudeva ;
Tomas-Loba, Antonia ;
Horejsi, Zuzana ;
Tan, Antoinette R. ;
Boulton, Simon J. ;
Ganesan, Shridar .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2013, 288 (45) :32357-32369
[13]   Differential effects of Th1 versus Th2 cytokines in combination with hypoxia on HIFs and angiogenesis in RA [J].
Larsen, Helene ;
Muz, Barbara ;
Khong, Tak L. ;
Feldmann, Marc ;
Paleolog, Ewa M. .
ARTHRITIS RESEARCH & THERAPY, 2012, 14 (04)
[14]   22222q MRP8 promotes Th17 differentiation via upregulation of IL-6 production by fibroblast-like synoviocytes in rheumatoid arthritis [J].
Lee, Dong-Gun ;
Woo, Jung-Won ;
Kwok, Seung-Ki ;
Cho, Mi-La ;
Park, Sung-Hwan .
EXPERIMENTAL AND MOLECULAR MEDICINE, 2013, 45 :e20-e20
[15]   MiR-141-3p promotes prostate cancer cell proliferation through inhibiting kruppel-like factor-9 expression [J].
Li, Jiu-zhi ;
Li, Jia ;
Wang, Hui-qin ;
Li, Xun ;
Wen, Bin ;
Wang, Yu-jie .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2017, 482 (04) :1381-1386
[16]   Circular RNA circ_0130438 suppresses TNF-α-induced proliferation, migration, invasion and inflammation in human fibroblast-like MH7A synoviocytes by regulating miR-130a-3p/KLF9 axis [J].
Li, Lei ;
Zhan, Minqing ;
Li, Mingwei .
TRANSPLANT IMMUNOLOGY, 2022, 72
[17]   Secreted Protein Acidic and Rich in Cysteine Mediated Biomimetic Delivery of Methotrexate by Albumin-Based Nanomedicines for Rheumatoid Arthritis Therapy [J].
Liu, Lu ;
Hu, Fanlei ;
Wang, Hui ;
Wu, Xiaoli ;
Eltahan, Ahmed Shaker ;
Stanford, Stephanie ;
Bottini, Nunzio ;
Xiao, Haihua ;
Bottini, Massimo ;
Guo, Weisheng ;
Liang, Xing-Jie .
ACS NANO, 2019, 13 (05) :5036-5048
[18]   The role and therapeutic implications of fibroblast-like synoviocytes in inflammation and cartilage erosion in rheumatoid arthritis [J].
Noss, Erika H. ;
Brenner, Michael B. .
IMMUNOLOGICAL REVIEWS, 2008, 223 :252-270
[19]  
Pap T, 2000, ARTHRITIS RHEUM, V43, P2531, DOI 10.1002/1529-0131(200011)43:11<2531::AID-ANR21>3.0.CO
[20]  
2-V
1234