Resveratrol inhibits Src tyrosine kinase, STAT3, and Wnt signaling pathway in collagen induced arthritis model Burak Oz 1 Ahmet Yildirim 2 Servet Yolbas 3 Zulfinaz Betul Celik 4 Ebru Onalan Etem 4 Gulnihal Deniz 5 Mustafa Akin 6 Zeynel Abidin Akar 1 Ahmet Karatas 1 * Suleyman Serdar Koca 1 1 Department of Rheumatology, Faculty of Medicine, Firat University, Elazig, Turkey 2 Department of Rheumatology, Elazig Education and Research Hospital, Elazı  g, Turkey 3 Department of Rheumatology, Faculty of Medicine, Inonu University, Malatya, Turkey 4 Department of Medical Biology, Faculty of Medicine, Firat University, Elazig, Turkey 5 Department of Anatomy, Faculty of Medicine, Firat University, Elazig, Turkey 6 Department of Pathology, Faculty of Medicine, Firat University, Elazig, Turkey Abstract Resveratrol, a phytochemical, acts several cellular signaling pathways and has anti-inflammatory potentials. The purpose of this study is to research the therapeutic effect of resveratrol in collagen-induced arthritis (CIA) model in rats and whether res- veratrol affects the activities of signaling pathways those are potent pathogenic actors of rheumatoid arthritis. Arthritis was induced by intradermal injection of chicken type II collagen combined with incomplete Freund’s adjuvant in Wistar albino rats. One day after the onset of arthritis (day 14), resveratrol (20 mg/kg/day) was given via oral gavage, until day 29. The paws of the rats were obtained for further analysis. Tissue Wnt5a, mitogen-activated protein kinase (MAPK), Src tyrosine kinase and signal transducer, and activator of transcription-3 (STAT3) mRNA expressions were determined by real-time poly- merase chain reaction. Resveratrol ameliorated the clinical and histopathological (perisynovial inflammation and cartilage- bone destruction) findings of inflammatory arthritis. The tissue mRNA expressions of Wnt5a, MAPK3, Src kinase, and STAT3 were increased in the sham group compared to the control group. Resveratrol supplement decreased their expressions. The present study shows that Src kinase, STAT3, and Wnt sig- naling pathway are active in the CIA model. Resveratrol inhibits these signaling pathways and ameliorates inflammatory arthri- tis. © 2018 BioFactors, 9999(9999):1–6, 2018 Keywords: rheumatoid arthritis; collagen induced arthritis; resveratrol Abbreviations: CIA, collagen-induced arthritis; COX-2, cyclooxygenase-2; DMARDs, disease-modifying anti-rheumatic drugs; FLS, fibroblast-like synovio- cyte; GSH, glutathione; GSK-3β, glycogen synthase kinase-3 beta; MALAT1, metastasis-associated lung adenocarcinoma transcript 1; MDA, malondialde- hyde; MMP, matrix metalloproteinase; PGE2, prostaglandin; PIAS, protein inhibitor of activated STAT; PTP, protein tyrosine phosphatases; RA, rheumatoid arthritis; RANKL, receptor activator of nuclear factor kappa-B ligand; SHP-2, SH2 domain-containing tyrosine phosphatase; SMAD, small mothers against decapentaplegic; STAT, signal transducer and activator of transcription; TNF-α, tumor necrosis factor; TRAIL, tumor necrosis factor-related apoptosis- inducing ligand; VSMC, vascular smooth muscle cells © 2018 International Union of Biochemistry and Molecular Biology Volume 9999, Number 9999, Month 2018, Pages 1–6 *Address for correspondence: Ahmet Karatas, Firat Universitesi, Tip Fakultesi, Romatoloji BD., 23119 Elazig, Turkey. Tel.: +90 424 2333555; Fax: +90 424 2388096; E-mail: drakaratas@yahoo.com. Received 10 July 2018; accepted 8 September 2018 DOI 10.1002/biof.1463 Published online 00 Month 2018 in Wiley Online Library (wileyonlinelibrary.com) BioFactors 1 Research Communication