SAG, a sonic hedgehog signaling agonist, alleviates anxiety behavior in high-fat diet-fed mice.

Anxiety is a prevalent and disabling psychiatric disorder. Mitochondrial dysfunction due to the high-fat diet (HFD) was regarded as a risk factor in the pathogenesis of anxiety. The Sonic hedgehog (SHH) pathway was known to improve mitochondrial dysfunction through antioxidant and anti-apoptotic effects on some neurological diseases. Nonetheless, its effect on anxiety has not been well studied. In this study, we aimed to explore whether SHH signaling pathway plays a protective role in anxiety by regulating mitochondrial homeostasis. SAG, a typical SHH signaling agonist, was administered intraperitoneally in HFD-fed mice. HFD-induced anxiety-like behavior in mice was confirmed using the open field and elevated plus maze tests. Immunofluorescence staining and Western blotting assays showed that the SHH signaling was downregulated in the prefrontal cortex neurons from HFD-fed mice. Electron microscopy results showed the mitochondria in the prefrontal cortex of HFD-fed mice were fragmented, which appeared small and spherical, and the area, perimeter and circularity of mitochondria were decreased. Mitofusin2 (Mfn2) and dynamin-related protein 1 (Drp1) were the key proteins involved in mitochondrial division and fusion. SAG treatment could rectify the imbalanced expression of Mfn2 and Drp1 in the prefrontal cortex of the HFD-fed mice, and alleviate the mitochondrial fragmentation. Furthermore, SAG decreased anxiety-like behavior in the HFD-fed mice. These findings suggested that SHH signal was neuroprotective in obesity and SAG relieved anxiety-like behavior through reducing mitochondrial fragmentation.

The LncRNA AK018453 regulates TRAP1/Smad signaling in IL-17-activated astrocytes: A potential role in EAE pathogenesis.

The pro-inflammatory cytokine interleukin 17 (IL-17), that is mainly produced by Th17 cells, has been recognized as a key regulator in multiple sclerosis (MS) and experimental autoimmune encephalomyelitis (EAE). Reactive astrocytes stimulated by proinflammatory cytokines including IL-17 are involved in blood brain barrier destruction, inflammatory cells infiltration and spinal cord injury. However, the role of long non-coding RNAs (lncRNAs) induced by IL-17 in the pathogenesis of MS and EAE remains unknown. Herein, we found that an IL-17-induced lncRNA AK018453 promoted TGF-ß receptor-associated protein 1 (TRAP1) expression and Smad-dependent signaling in mouse primary astrocytes. Knockdown of AK018453 significantly suppressed astrocytosis, attenuated the phosphorylation of Smad2/3, reduced NF-κB p65 and CBP/P300 binding to the TRAP1 promoter, and diminished pro-inflammatory cytokine production in the IL-17-treated astrocytes. AK018453 knockdown in astrocytes by a lentiviral vector in vivo dramatically inhibited inflammation and prevented the mice from demyelination in the spinal cord during the progression of EAE. Together, these results suggest that AK018453 regulates IL-17-dependent inflammatory response in reactive astrocytes and potentially promotes the pathogenesis of EAE via the TRAP1/Smad pathway. Targeting this pathway may have a therapeutic potential for intervening inflammatory demyelinating diseases.

Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection.

As a small DNA virus, hepatitis B virus (HBV) plays a pivotal role in the development of various liver diseases, including hepatitis, cirrhosis, and liver cancer. Among the molecules encoded by this virus, the HBV X protein (HBX) is a viral transactivator that plays a vital role in HBV replication and virus-associated diseases. Accumulating evidence so far indicates that pattern recognition receptors (PRRs) are at the front-line of the host defense responses to restrict the virus by inducing the expression of interferons and various inflammatory factors. However, depending on HBX, the virus can control PRR signaling by modulating the expression and activity of essential molecules involved in the toll-like receptor (TLR), retinoic acid inducible gene I (RIG-I)-like receptor (RLR), and NOD-like receptor (NLR) signaling pathways, to not only facilitate HBV replication, but also promote the development of viral diseases. In this review, we provide an overview of the mechanisms that are linked to the regulation of PRR signaling mediated by HBX to inhibit innate immunity, regulation of viral propagation, virus-induced inflammation, and hepatocarcinogenesis. Given the importance of PRRs in the control of HBV replication, we propose that a comprehensive understanding of the modulation of cellular factors involved in PRR signaling induced by the viral protein may open new avenues for the treatment of HBV infection.

Calcium signaling in hepatitis B virus infection and its potential as a therapeutic target.

As a ubiquitous second messenger, calcium (Ca2+) can interact with numerous cellular proteins to regulate multiple physiological processes and participate in a variety of diseases, including hepatitis B virus (HBV) infection, which is a major cause of hepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. In recent years, several studies have demonstrated that depends on the distinct Ca2+ channels on the plasma membrane, endoplasmic reticulum, as well as mitochondria, HBV can elevate cytosolic Ca2+ levels. Moreover, within HBV-infected cells, the activation of intracellular Ca2+ signaling contributes to viral replication via multiple molecular mechanisms. Besides, the available evidence indicates that targeting Ca2+ signaling by suitable pharmaceuticals is a potent approach for the treatment of HBV infection. In the present review, we summarized the molecular mechanisms related to the elevation of Ca2+ signaling induced by HBV to modulate viral propagation and the recent advances in Ca2+ signaling as a potential therapeutic target for HBV infection. Video Abstract.

The impact of Clonorchis sinensis infection on immune response in mice with type II collagen-induced arthritis.

BACKGROUND: Clonorchis sinensis infection could trigger strong immune responses in mice and humans. However, whether the C.sinensis infection has an impact on arthritis is unknown. Here we investigated the effect of C.sinensis infection on type II collagen-induced arthritis in BALB/c mice. RESULTS: The mice were firstly infected with 45 C.sinensis metacercariae by oral gavage. Four weeks later, arthritis in mice was induced by type II collagen. Joint inflammation with severe redness and swelling in hind paws was observed in type II collagen-induced arthritis (CIA) mice. Besides, the physical activity was significantly reduced, but the respiratory exchange ratio was increased in CIA mice. Compared with CIA mice, C.sinensis infection could increase the severity of arthritis in CIA mice, based on the results of disease score and pathological changes. Compared to CIA mice, increased neutrophils and Ly6Chi monocytes, decreased B cells and CD4+T cells, were found in C.sinensis infected CIA mice. Besides these, C.sinensis infected mice also displayed significantly higher levels of serum IL-4 and IL-17 than those in CIA mice. CONCLUSIONS: Taken together, our data suggest that C.sinensis infection have a bad effect on arthritis, and could induce the abnormality of the immune response in mice with CIA.

Downregulation of sonic hedgehog signaling in the hippocampus leads to neuronal apoptosis in high-fat diet-fed mice.

BACKGROUND/AIMS: Obesity induces hippocampal neuronal apoptosis and leads to cognitive function deficits. Sonic hedgehog (SHH) signaling is crucial during nervous system development and is neuroprotective in many neurologic diseases. This study assessed the role of SHH signaling in the cognitive deficits in high-fat diet (HFD)-induced obese mice. METHODS: Flow cytometry assay was used to examine cell apoptosis. Tissue pathology was evaluated by Nissl staining. Immunofluorescent staining and western blotting were used to detect SHH signaling molecules and apoptosis-related proteins. The Morris water maze test was performed to evaluate mouse spatial learning and memory. RESULTS: After HFD feeding for 24 weeks, the expression of SHH signaling molecules was downregulated in the mouse hippocampus. In vitro, GANT61 inhibited SHH signaling and induced apoptosis in HT22 mouse hippocampal cells. Smoothened agonist (SAG), an agonist of SHH signaling, reduced apoptosis in GANT61-treated HT22 cells by regulating caspase-9 and caspase-3 activation. In vivo, 12-week SAG treatment also inhibited the apoptosis of hippocampal neurons in HFD-fed mice by increasing mitofusin 2 (Mfn2) and B-cell lymphoma 2 (Bcl-2) levels and decreasing dynamin-related protein 1 (Drp1) and Bcl-2 homologous antagonist/killer (Bak) levels. Behavioral testing showed that SAG administration ameliorated the cognitive impairment in HFD-fed mice. CONCLUSION: Downregulation of hippocampal SHH signaling leads to neuronal apoptosis and cognitive deficits in HFD-fed mice. These findings provide useful information for the identification of potential targets for research and therapeutic interventions for cognitive impairment in obesity.

GANT61 alleviates arthritic symptoms by targeting fibroblast-like synoviocytes in CIA rats.

BACKGROUND: Studies have identified that the fibroblast-like synoviocytes (FLS) exhibited tumor-like characteristics and was the key factor in the pathogenesis of Rheumatoid arthritis (RA). GANT61, an antagonist of the sonic hedgehog pathway, has been verified with inhibitory effect on many cancers. Here we investigated the effect of GANT61 on FLS and the development of collagen-induced arthritis (CIA). METHODS: 40 Sprague Dawley (SD) rats were randomly divided into four groups: normal, CIA, CIA+10 mg/kg GANT61 and CIA+20 mg/kg GANT61. CIA was induced in rat with collagen injecting. The GANT61 was administered by intraperitoneal injection every 2 days for 3 weeks. The CIA model was identified with the paw swelling, arthritis score and the pathologic changes in joint. The FLS of different group were primary cultured. The proliferative capacity of FLS was detecteded via Cell Counting Kit-8 (CCK-8) method, and the apoptosis was detecteded by flow cytometry. The Bcl-2, Bax, Caspases3 and cleaved Caspases3 in synovium and FLS were detecteded by Western Blot. RESULTS: The 20 mg/kg GANT61 treatment reduced the incidence of CIA and relieved the arthritis symptoms in CIA rats. The Bcl-2 was upregulated and the Bax was downregulated in the CIA rats synovium. The 10 mg/kg and 20 mg/kg GANT61 diminished the Bcl-2 expression, 20 mg/kg GANT61 increased the Bax and activated the Caspases3 in the CIA synovium. The proliferation of CIA-FLS was significantly higher and the apoptosis of the CIA-FLS was lower than that of the control group. The 10 mg/kg and 20 mg/kg GANT61 treatment can reduce cell proliferation and induce apoptosis by diminishing Bcl-2 and increasing the Bax in CIA-FLS. CONCLUSIONS: The GANT61 inhibit the proliferation of FLS and alleviated the arthritic symptoms in CIA rats, this implied the GANT61 may be recommended as a possible candidate for the therapy of RA.

Purple sweet potato color improves hippocampal insulin resistance via down-regulating SOCS3 and galectin-3 in high-fat diet mice.

Hippocampal insulin resistance is the key factor in cognitive deficits. The obesity induces chronic inflammation and the inflammation molecules suppressors of cytokine signaling3 (SOCS3) and galectin-3 directly impair the insulin signaling. The anti-inflammation properties of purple sweet potato color (PSPC) prompted us to investigate the effect of PSPC on cognitive impairment associated with obesity. 60 C57BL/6 mice were randomly divided into four groups: normal, high fat diets (HFD), HFD+PSPC and PSPC. The mice were fed with the HFD or normal diet for 32 weeks. The PSPC (500 mg/kg/day) was administered via oral gavage from 21 to 32 weeks. The results showed the PSPC rectified the abnormal metabolism indexes induced by HFD, including ameliorated obesity, decreased the concentration of fasting blood glucose and improved the glucose tolerance. The Morris water maze test showed the PSPC alleviated the cognitive impairment in HFD mice. The PSPC decreased the expression of Iba1, tumor necrosis factor-α, interleukin-1ß, SOCS3 and galectin-3 in hippocampus of HFD mice. The insulin signaling molecules including the p-IRS1 (Tyr608), PI3K p110α and p-AKT (Ser473) were detected and the PSPC treatment improved the insulin resistance in hippocampus of HFD mice. Furthermore, the PSPC increased Bcl-2, diminished the Bak and the cleaved-caspase3 in HFD mice hippocampus. These findings indicated that PSPC could be a potential treatment to improve the cognitive impairment associated with obesity.

Analysis of Long Noncoding RNA and mRNA Expression Profiles in IL-9-Activated Astrocytes and EAE Mice.

BACKGROUND/AIMS: Multiple sclerosis (MS) is an autoimmune disease in the central nervous system associated with demyelination and axonal injury. Astrocyte activation is involved in the pathogenesis of MS and experimental autoimmune encephalomyelitis (EAE), an animal model of MS. This study was designed to find potential lncRNAs in EAE mice and activated astrocytes. METHODS: we performed microarray analysis of lncRNAs from the brain tissues of EAE mice and primary mouse astrocytes treated with IL-9(50 ng/ml). 12 lncRNAs were validated through real-time PCR. Gene ontology and KEGG pathway analysis were applied to explore the potential functions of lncRNAs. RESULTS: Differentially expressed 3300 lncRNAs and 3250 mRNAs were in the brain tissues of EAE mice, and 3748 lncRNAs and 3332 mRNAs were in activated astrocytes. Notably, there were 2 co-up-regulated lncRNAs and 3 co-down-regulated lncRNAs both in the brain tissues of EAE mice and in activated astrocytes, including Gm14005, Gm12478, mouselincRNA1117, AK080435, and mouselincRNA0681, which regulate the ER calcium flux kinetics, zinc finger protein and cell apoptosis. Similarly, there were 7 mRNAs co-up-regulated and 2 mRNAs co-down-regulated both in vivo and in vitro. Gene ontology and KEGG pathway analysis showed that the biological functions of differentially expressed mRNAs were associated with metabolism, development and inflammation. The results of realtime PCR validation were consistent with the data from the microarrays. CONCLUSIONS: Our data uncovered the expression profiles of lncRNAs and mRNAs in vivo and in vitro, which may help delineate the mechanisms of astrocyte activation during MS/EAE process.

Polyene Phosphatidylcholine inhibited the inflammatory response in LPS-stimulated macrophages and ameliorated the adjuvant-induced rat arthritis.

This study sought to investigate the anti-inflammatory effect of Polyene Phosphatidylcholine (PPC), a clinical drug that is used to treat hepatopathy, on lipopolysaccharide (LPS)-stimulated macrophages and on bovine collagen II-induced arthritis (CIA) rats. In stimulated primary and Raw264.7 macrophages by LPS, PPC significantly down-regulated the relative expression of mRNA such as IL-6, TNF-α, TLR-2, TLR-4, MyD88, and NF-κB while up-regulated IL-10 and TGF-ß expression. Moreover, the concentration of IL-6, TNF-α, IL-10, and TGF-ß in the cultured supernatants showed the similar tendency with their mRNA alterations. In addition, PPC could significantly inhibit the LPS-induced expression of MyD88 and NF-κB p65 in both mRNA and protein levels. These results suggest that PPC could down-regulate the LPS-stimulated inflammation in macrophages through TLR-2/TLR-4/MyD88/NF-κB pathway in vitro. Furthermore, to explore its effects in vivo, PPC was administrated to CIA rats. In comparison to CIA group, PPC-treated rats showed decreased arthritis score and osteopenia. Besides, PPC exhibited its ability to alleviate the degree of synovial hyperplasia, inflammatory cell infiltration, and destruction of cartilage and bone, thus remarkably improving the condition of CIA rats. In short, this study demonstrated that PPC had the potential to be an anti-inflammatory drug to treat inflammatory disorders such as rheumatoid arthritis.

Gabapentin regulates expression of FGF2 and FGFR1 in dorsal root ganglia via microRNA-15a in the arthritis rat model.

BACKGROUND: Arthritis is an inflammatory disease with a prevalence rate of approximately 10% in China, which commonly manifests as pain. The aim of the current study was to investigate the function of gabapentin in the dorsal root ganglion in an arthritis rat model, and assess the effect of gabapentin on the expression of fibroblast growth factor 2 (FGF2) and FGF receptor 1 (FGFR1). METHODS: A total of 30 healthy male Sprague-Dawley rats were randomly divided into the following three groups: Untreated group, control group and gabapentin group. Rats in the control and the gabapentin groups were injected with Freund's complete adjuvant to induce arthritis. A total of 7 days subsequent to model establishment, the gabapentin group was administered intraperitoneally gabapentin for 8 days. The alterations in thickness of paw pad and paw withdrawal mechanical threshold (PWMT) were detected, which indicated that the rats in the control and gabapentin groups presented with the symptoms of arthritis. RESULTS: In the control group, the PWMT value was significantly reduced (P < 0.05), whereas the PWMT value was significantly increased in the gabapentin group. Immunohistochemistry demonstrated that the expression levels of FGF2 and FGFR1 were increased in the control group compared with the untreated group, while the expression levels of FGF2 and FGFR1 were reduced in the gabapentin group. Moreover, the FGF2 antagonist PD173074 partially improved the plantar thickness and PWMT of the arthritic rats. Bioinformatics analysis predicted microRNA-15a binding sites in the 3'untranslated regions (UTR) of FGF2 and FGFR1. Furthermore, the expression of microRNA-15a was reduced in the control group compared with untreated rats, whereas microRNA-15a in the gabapentin group was upregulated compared with the control. Additionally, the luciferase reporter assay confirmed that microRNA-15a could inhibit the protein expression through pairing with the 3'UTR of FGF2 and FGFR1 mRNAs. CONCLUSION: Gabapentin may relieve arthritis pain and reduce the expression of FGF2 and FGFR1 in dorsal root ganglia. Furthermore, microRNA-15a may be involved in the regulatory process.

The Inhibitory Effects of Purple Sweet Potato Color on Hepatic Inflammation Is Associated with Restoration of NAD⁺ Levels and Attenuation of NLRP3 Inflammasome Activation in High-Fat-Diet-Treated Mice.

Purple sweet potato color (PSPC), a class of naturally occurring anthocyanins, exhibits beneficial effects on metabolic syndrome. Sustained inflammation plays a crucial role in the pathogenesis of metabolic syndrome. Here we explored the effects of PSPC on high-fat diet (HFD)-induced hepatic inflammation and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + PSPC group, and PSPC group. PSPC was administered by daily oral gavage at doses of 700 mg/kg/day for 20 weeks. Nicotinamide riboside (NR) was used to increase NAD⁺ levels. Our results showed that PSPC effectively ameliorated obesity and liver injuries in HFD-fed mice. Moreover, PSPC notably blocked hepatic oxidative stress in HFD-treated mice. Furthermore, PSPC dramatically restored NAD⁺ level to abate endoplasmic reticulum stress (ER stress) in HFD-treated mouse livers, which was confirmed by NR treatment. Consequently, PSPC remarkably suppressed the nuclear factor-κB (NF-κB) p65 nuclear translocation and nucleotide oligomerization domain protein1/2 (NOD1/2) signaling in HFD-treated mouse livers. Thereby, PSPC markedly diminished the NLR family, pyrin domain containing 3 (NLRP3) inflammasome activation, ultimately lowering the expressions of inflammation-related genes in HFD-treated mouse livers. In summary, PSPC protected against HFD-induced hepatic inflammation by boosting NAD⁺ level to inhibit NLRP3 inflammasome activation.

Attenuation of hepatic steatosis by purple sweet potato colour is associated with blocking Src/ERK/C/EBPß signalling in high-fat-diet-treated mice.

Our previous work showed that purple sweet potato colour (PSPC), a class of naturally occurring anthocyanins, effectively improved hepatic glucose metabolic dysfunction in high-fat-diet (HFD)-treated mice. This study investigated the effects of PSPC on HFD-induced hepatic steatosis and the signalling events associated with these effects. Mice were divided into 4 groups: control group, HFD group, HFD+PSPC group, and PSPC group. PSPC was administered daily for 20 weeks at oral doses of 700 mg/(kg·day)-1). Our results showed that PSPC significantly improved obesity and related metabolic parameters, as well as liver injury in HFD-treated mice. Moreover, PSPC dramatically attenuated hepatic steatosis in HFD-treated mice. PSPC markedly prevented oxidative stress-mediated Src activation in HFD-treated mouse livers. Furthermore, PSPC feeding remarkably suppressed mitogen-activated protein kinase kinase/extracellular-signal-regulated kinase (MEK/ERK) signalling and consequent CCAAT/enhancer binding protein ß (C/EBPß) activation and restored AMPK activation in HFD-treated mouse livers, which was confirmed by U0126 treatment. Ultimately, PSPC feeding dramatically reduced protein expression of FAS and CD36 and the activation of ACC, and increased the protein expression of CPT1A in the livers of HFD-treated mice, indicating decreased lipogenesis and fatty acid uptake and enhanced fatty acid oxidation. In conclusion, PSPC exhibited beneficial effects on hepatic steatosis, which were associated with blocking Src and C/EBPß activation.

Genetic diversity and phylogenetic analysis of EG95 sequences of Echinococcus granulosus: Implications for EG95 vaccine application.

OBJECTIVE: To analyse the genetic variability of EG95 sequences and provide guidance for EG95 vaccine application against Echinococcus granulosus (E. granulosus). METHODS: We analysed EG95 polymorphism by collecting total 97 different E. granulosus isolates from 12 different host species that originated from 10 different countries. Multiple sequence alignments and the homology were performed by Lasergene 1 (DNASTAR Inc., Madison, WI), and the phylogenetic analysis was performed by using MEGA5.1 (CEMI, Tempe, AZ, USA). In addition, linear and conformational epitopes were analysed, including secondary structure, NXT/S glycosylation, fibronectin type III (FnIII) domain and glycosylphosphatidylinositol anchor signal (GPI-anchor). The secondary structure was predicted by PSIPRED method. RESULTS: Our results indicated that most isolates overall shared 72.6-100% identity in EG95 gene sequence with the published standard EG95 sequence, X90928. However, EG95 gene indeed has polymorphism in different isolates. Phylogenetic analysis showed that different isolates could be divided into three subgroups. Subgroup 1 contained 87 isolates while Subgroup 2 and Subgroup 3 consisted of 3 and 7 isolates, respectively. Four sequences cloned from oncosphere shared a high identity with the parental sequence of the current vaccine, X90928, and they belonged to Subgroup 1. However, in comparison to X90928, several amino acid mutations occurred in most isolates besides oncosphere, which potentially altered the immunodominant linear epitopes, glycosylation sites and secondary structures in EG95 genes. All these variations might change their previous antigenicity and thereby affecting the efficacy of current EG95 vaccine. CONCLUSIONS: This study reveals the genetic variability of EG95 sequences in different E. granulosus isolates, and proposed that more vaccination trials would be needed to test the effectiveness of current EG95 vaccine against distinct isolates in different countries.

[Sonic hedgehog (SHH) promotes the proliferation of synovial fibroblasts of rats with collagen-induced arthritis].

OBJECTIVE: To investigate the effect of sonic hedgehog (SHH) on the proliferation of synovial fibroblasts (SFs). METHODS: The serum samples were collected from 30 rheumatoid arthritis (RA) patients, 30 systemic lupus erythematosus (SLE) patients, 30 ankylosing spondylitis (AS) patients and 30 healthy subjects. The concentrations of serum SHH were detected by ELISA. Collagen induced arthritis (CIA) were developed by type 2 collagen in Sprague-Dawley rats. The SFs were isolated from knee synovial tissues of CIA rats, and then identified by the detection of vimentin by immunofluorescence technique. Before and 72 hours after blocking SHH-glioma-associated oncogene 1 (Gli-1) signaling pathway with GANT61, the expression level of SHH in SFs was detected by Western blotting, and the proliferation of SFs was examined with CCK-8 assay. RESULTS: The level of serum SHH in the RA patients was remarkably higher than that in the SLE, AS patients and the healthy controls. In the CIA rats, the expression of SHH in SFs in vitro was higher than that in the healthy control rats. After 72-hour treatment of GANT61 to block SHH-Gli-1 signaling pathway, the expression level of SHH protein in SFs from CIA rats was reduced, and meanwhile the proliferation of the SFs was inhibited. CONCLUSION: SHH plays an important role in the proliferation of SFs and could be used as a potential therapeutic target for RA.

The Effect of SHH-Gli Signaling Pathway on the Synovial Fibroblast Proliferation in Rheumatoid Arthritis.

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.