title: The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.
abstract: Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by chronic synovitis. This study aims to investigate the role of sonic hedgehog (SHH)-Gli signaling pathway in synovial fibroblast proliferation in rheumatoid arthritis. The expression of serum SHH in RA patients group was significantly increased compared with the systemic lupus erythematosus (SLE), ankylosing spondylitis (AS), and healthy subject (healthy control, HC) groups, respectively; serum SHH expression of RA patients was positively correlated with rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (anti-CCP Ab), while there was no significant correlation between SHH expression and erythrocyte sedimentation rate (ESR). SHH, Ptch, Smo, and Gli molecules were highly expressed in rat RA-synovial fibroblast (RA-SF); after blocking the SHH-Gli signaling pathway with a Gli specific inhibitor, Gli-antagonist 61 (GANT61), RA-SF proliferation was inhibited in a dose-dependent manner and the apoptosis rate of RA-SF was increased as well; the expression levels of fibroblast growth factor receptor 1 (FGFR1) and FGFR3 declined in SF cells after GANT61 treatment. Our results suggest that SHH-Gli pathway is involved in the pathogenesis of RA, and blocking SHH-Gli pathway inhibits RA-SF cell proliferation and increases cell apoptosis, which may shed light on developing new ideas for RA treatment.
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Suping
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Human Anatomy, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
authors.forename: Dexu
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Yan
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. tangrenxian_2015@163.com.
authors.forename: Renxian
authors.initials: R
authors.lastname: Tang
authors.affiliation: Department of pathogenic biology and Immunology, Xuzhou Medical College, 209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. lxmlxm_hi@126.com.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D017209:Apoptosis / Q000502:physiology*; D001169:Arthritis, Experimental / Q000473:pathology*; D001172:Arthritis, Rheumatoid / Q000473:pathology*; D001323:Autoantibodies / Q000097:blood; D001799:Blood Sedimentation; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D053823:Hedgehog Proteins / Q000097:blood* / Q000378:metabolism*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000473:pathology; D000072081:Patched-1 Receptor / Q000378:metabolism; D010456:Peptides, Cyclic / Q000276:immunology; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000096:biosynthesis; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000096:biosynthesis; D012217:Rheumatoid Factor / Q000097:blood; D015398:Signal Transduction; D000072086:Smoothened Receptor / Q000378:metabolism; D013167:Spondylitis, Ankylosing / Q000473:pathology; D000070918:Synoviocytes / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D000906:Antibodies; D001323:Autoantibodies; C551027:GANT 61; C498521:Gli1 protein, rat; D053823:Hedgehog Proteins; D000072081:Patched-1 Receptor; D010456:Peptides, Cyclic; C000606239:Ptch1 protein, rat; D011725:Pyridines; D011743:Pyrimidines; C509239:SHH protein, human; C546888:Shh protein, rat; C498555:Smo protein, rat; D000072086:Smoothened Receptor; D000071676:Zinc Finger Protein GLI1; C487763:cyclic citrullinated peptide; C069820:Fgfr3 protein, rat; D012217:Rheumatoid Factor; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1; D051498:Receptor, Fibroblast Growth Factor, Type 3
keywords: SHH-Gli signaling pathway; proliferation; rheumatoid arthritis; synovial fibroblast