title: Interleukin 34 Upregulation Contributes to the Increment of MicroRNA 21 Expression through STAT3 Activation Associated with Disease Activity in Rheumatoid Arthritis.
abstract: Interleukin 34 (IL-34) and microRNA 21 (miR-21) were found to be involved in the pathological process of rheumatoid arthritis (RA), but the details were unclear. In this study, we aimed to clarify the relationship between IL-34 and miR-21 in RA.
  
  
  
  IL-34 concentrations in serum and synovial fluid (SF) of patients with RA were measured by ELISA. Fibroblast-like synovial cells (FLS) were cultured for evaluation of STAT3 activation, miR-21, and Bax/Bcl-2 expression by Western blot and real-time PCR. Correlations were analyzed between clinical features and detectable variables including SF IL-34 levels and miR-21 expression.
  
  
  
  SF IL-34 levels were significantly higher in patients with RA who had a high 28-joint Disease Activity Score (DAS28 ≥ 3.2) than in those with a lower DAS28 (DAS28 < 3.2). DAS28 scores and miR-21 expression in FLS had a significant positive correlation with the SF IL-34 levels. In addition, IL-34 stimulation strengthened the activation of p-STAT3, resulting in the increment of miR-21 expression. Inhibiting of miR-21 expression contributed to decreased Bcl-2/Bax ratio, suggesting that miR-21 was involved in the resistance to apoptosis. With the blocking of the colony-stimulating factor-1 receptor (CSF1R), decreased protein expressions including CSF1R, p-STAT3/STAT3, and Bcl-2/Bax were shown, suggesting that CSF1R participated in the biological functions of IL-34 in RA.
  
  
  
  The IL-34/STAT3/miR-21 pathway is crucial for the survival of synovial fibroblasts in RA, which might be candidate therapeutic targets for RA treatment.
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology.
authors.forename: Sisi
authors.initials: S
authors.lastname: Yang
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology.
authors.forename: Shujun
authors.initials: S
authors.lastname: Jiang
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology.
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology.
authors.forename: Shenghao
authors.initials: S
authors.lastname: Tu
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology. wangzhigang1979@hotmail.com zhepi2006@163.com.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: From the Department of Geriatrics, and Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine, Wuhan, China.S. Yang, PhD, Department of Geriatrics, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Jiang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Y. Wang, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; S. Tu, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology; Z. Wang, PhD, Department of Pathogen Biology, Basic Medical College, Hubei University of Chinese Medicine; Z. Chen, PhD, Department of Integrated Chinese Traditional and Western Medicine, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology. wangzhigang1979@hotmail.com zhepi2006@163.com.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000328:Adult; D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D015854:Up-Regulation
chemical_list: C529076:IL34 protein, human; D007378:Interleukins; C524940:MIRN21 microRNA, human; D035683:MicroRNAs; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human
keywords: COLONY-STIMULATING FACTOR-1 RECEPTOR; INTERLEUKIN 34; MICRORNA 21; RHEUMATOID ARTHRITIS; STAT3