Although angiogenesis-osteogenesis coupling is important in ankylosing spondylitis (AS), therapeutic agents targeting the vasculature remain elusive. Here, we identified activating transcription factor 6 (ATF6) as an important regulator of angiogenesis in AS patients. Firstly, we found that ATF6 and fibroblast growth factor 2 (FGF2) levels were higher in SKG mice and AS patient cartilage. The pro-angiogenic ability of human chondrocytes was enhanced through activated ATF6-FGF2 axis following long-term stimulation with inflammatory factors, e.g. TNF-α, IFN-γ or IL-17. Mechanistically, ATF6 interacted with the FGF2 promotor and promoted its transcription. Treatment with the ATF6 inhibitor Ceapin-A7 inhibited angiogenesis in vitro and angiogenesis-osteogenesis coupling in vivo. ATF6 may aggravate angiogenesis-osteogenesis coupling during AS by mediating FGF2 transcription in chondrocytes, implying that ATF6 represents a promising therapeutic target for AS.

中文翻译：

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ATF6通过介导软骨细胞中FGF2的表达加重强直性脊柱炎期间加重血管生成-成骨耦合

尽管血管生成-成骨耦合在强直性脊柱炎（AS）中很重要，但靶向血管的治疗剂仍然难以捉摸。在这里，我们确定了激活转录因子6（ATF6）是AS患者血管新生的重要调节剂。首先，我们发现SKG小鼠和AS患者软骨中的ATF6和成纤维细胞生长因子2（FGF2）水平较高。在炎性因子（例如TNF-α，IFN-γ或IL-17）长期刺激后，通过激活的ATF6-FGF2轴增强了人类软骨细胞的促血管生成能力。从机理上讲，ATF6与FGF2启动子相互作用并促进其转录。用ATF6抑制剂Ceapin-A7进行的体外抑制血管生成和体内血管生成与成骨耦合。ATF6可能通过介导软骨细胞中的FGF2转录而加重AS期间的血管生成-成骨耦合，这暗示ATF6代表AS的有希望的治疗靶标。