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Autoimmune hepatitis (AIH) is a chronic inflammatory liver disease with unknown etiology. CCN1, an extracellular matrix-associated protein, is associated with carcinoma, inflammation, liver fibrosis, and even autoimmune diseases. However, the role that CCN1 plays in AIH has remained undetermined. In this study, expression of CCN1 in liver was detected by real-time PCR, western blot and immunohistochemistry (IHC). CCN1 level in serum was detected by ELISA. Diagnostic value of CCN1 was determined by receiver operating characteristic (ROC) curve analysis. CCN1 conditional knockout (CCN1fl/flCre+) mice were generated by mating CCN1fl/fl C57BL/6J and CAG-Cre-ERT C57BL/6J mice. Autoimmune hepatitis mice model was induced by concanavalin A (ConA). IKKα/β, IκBα, NF-κB p65 and Akt phosphorylation were determined by western blot. NF-κB p65 nuclear translocation was examined by immunofluorescence. Here, we found that CCN1 was over-expressed in hepatocytes of AIH patients. CCN1 level also increased in serum of AIH patients compared to healthy controls (HC). ROC curve analysis results showed that serum CCN1 was able to distinguish AIH patients from HD. In ConA induced hepatitis mice model, CCN1 conditional knockout (CCN1fl/flCre+) attenuated inflammation by reducing ALT/AST level and IL-6 expression. In vitro, CCN1 treatment dramatically induced IL-6 production in LO2 cells. Moreover, the production of IL-6 was attenuated by CCN1 knockdown. Furthermore, we showed that CCN1 could activate IL-6 production via the PI3K/Akt/NF-κB signaling pathway by binding to α6β1 receptor. In summary, our results reveal a novel role of CCN1 in promoting inflammation by upregulation of IL-6 production in AIH. Our study also suggests that targeting of CCN1 may represent a novel strategy in AIH treatment.

Aim Gut microbiota play an important role in rheumatoid arthritis (RA). Biological therapies targeting tumor necrosis factor‐α (TNF‐α) have been used for treatment in RA patients. However, whether TNF‐α antagonist has some influence on gut microbiota is still unknown. This study aims to investigate the distribution of gut microbiota in collagen‐induced arthritis (CIA) mice treated with the TNF‐α antagonist etanercept. Methods Collagen‐induced arthritis mice were induced by type II collagen. Cytokine expression was detected by real‐time polymerase chain reaction. 16S ribosomal RNA sequencing was performed to characterize the gut microbiota in CIA mice treated with vehicle or etanercept. Sequencing reads were processed by Microbial Ecology software program. Results Compared with vehicle‐treated mice, we showed that CIA mice treated with etanercept led to attenuation of inflammation and reduced expression of TNF‐α, interferon (IFN)‐γ, interleukin (IL)‐6 and IL‐21. Meanwhile, results showed operational taxonomic units, richness estimators and the diversity indices of gut microbiota in etanercept‐treated mice were lower than that in vehicle‐treated mice. Moreover, bacterial abundance analyses showed that genus Escherichia/Shigella was more abundant in etanercept‐treated mice, and Lactobacillus, Clostridium XlVa, Tannerella were less abundant. The altered bacterial genus was correlated with TNF‐α, IFN‐γ, IL‐6, IL‐21 and IL‐10. Conclusion Our results revealed that TNF‐α antagonist treatment can reduce the abundance and diversity of gut microbiota in CIA mice. Targeted gut microbiota may be a new therapeutic strategy for the treatment of RA.

ObjectiveEarly and correct diagnosis would be beneficial for outcomes of rheumatoid arthritis (RA), but there are some limitations in current diagnostic tools. In this study, we aimed to evaluate the diagnostic value of circulating miR-22-3p and let-7a-5p in RA. MethodsSeventy-six RA patients, 30 systemic lupus erythematosus patients, 32 Sjögren's syndrome patients and 36 healthy donors recruited at the First Affiliated Hospital of Fujian Medical University (China) were included in this study. in plasma were measured using reverse transcriptase quantitative PCR and serum cytokines were detected by cytometric bead array. The participants' clinical materials were also collected. Receiver operating characteristic curve analysis and correlation analysis were performed to assess the potential value of circulating miRNAs in RA. Results Circulating miR-22-3p and let-7a-5p are significantly increased in RA patients and able to distinguish RA patients from other populations. Circulating let-7a-5p has been shown to improve the diagnostic ability of current laboratory indicators anti-cyclic citrullinated peptide antibodies and rheumatoid factor. Moreover, the discriminatory capacityof both circulating miRNAs contribute to complement the diagnosis for seronegative RA. Meanwhile, correlation analysis reveals that circulating miR-22-3p positively correlates with haemoglobin, serum bilirubin, albumin and IL-17 but negatively correlates with mean platelet volume as well as let-7a-5p. ConclusionThe increased circulating miR-22-3p and let-7a-5p levels in RA patients, especially in seronegative RA patients, may provide potential promising diagnostic biomarkers for RA in clinical practice.