Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway
Abstract Purpose Leucine-rich repeat-containing 15 (LRRC15) is a transmembrane protein that is highly expressed in the synovium of patients with rheumatoid arthritis (RA). Brevilin A (BrA), an active compound isolated from Centipeda minima, exerts potent anti-inflammatory effects. However, the anti-...
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BMC
2025-08-01
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| Series: | Arthritis Research & Therapy |
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| Online Access: | https://doi.org/10.1186/s13075-025-03629-1 |
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| author | Zhiping Qiao Qiqi Meng Bixia Xiao Yulei Long Qi Liang Tao Su |
| author_facet | Zhiping Qiao Qiqi Meng Bixia Xiao Yulei Long Qi Liang Tao Su |
| author_sort | Zhiping Qiao |
| collection | DOAJ |
| description | Abstract Purpose Leucine-rich repeat-containing 15 (LRRC15) is a transmembrane protein that is highly expressed in the synovium of patients with rheumatoid arthritis (RA). Brevilin A (BrA), an active compound isolated from Centipeda minima, exerts potent anti-inflammatory effects. However, the anti-RA effect of BrA and its underlying mechanism of action of BrA have not been fully elucidated. Methods Transcriptome analysis was performed to explore biomarkers of RA. An lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, a TNF-α-stimulated RA fibroblast-like synoviocytes (RA-FLSs) model, as well as a collagen-induced arthritis (CIA) rat model were used to explore the anti-RA effects of BrA. Moreover, inhibition or overexpression of LRRC15 was performed to explore the role of LRRC15 signaling in the anti-RA effects of BrA. Results Transcriptome analysis of patients with RA revealed that LRRC15 expression was significantly upregulated in the synovial tissue of RA patients. BrA significantly downregulated the expression of inflammation-related markers in cell models, and inhibited their proliferation and migration; Moreover, it significantly reduced joint swelling and cartilage damage in CIA rats. Further mechanistic studies suggest that inhibition of LRRC15 inhibits cell proliferation and migration; and overexpression of LRRC15 increases the protein levels of STAT3’s downstream metastasis-related markers. Conclusions Our findings suggest that BrA, a novel LRRC15 inhibitor, has promising anti-RA activity and potently inhibits LRRC15/STAT3 signaling pathway both in vivo and in vitro. This study not only supports the development of BrA as a novel therapeutic agent for RA treatment, but also paves the way for the development of other LRRC15-targeting therapeutic strategies. |
| format | Article |
| id | doaj-art-e8da4dda7b704da786e47fce7dc18ca7 |
| institution | Kabale University |
| issn | 1478-6362 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Arthritis Research & Therapy |
| spelling | doaj-art-e8da4dda7b704da786e47fce7dc18ca72025-08-24T11:42:17ZengBMCArthritis Research & Therapy1478-63622025-08-0127111310.1186/s13075-025-03629-1Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathwayZhiping Qiao0Qiqi Meng1Bixia Xiao2Yulei Long3Qi Liang4Tao Su5State Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineDepartment of Pharmacy, Shenzhen Bao’an Traditional Chinese Medicine Hospital, Guangzhou University of Chinese MedicineState Key Laboratory of Traditional Chinese Medicine Syndrome, Guangdong Key Laboratory for Translational Cancer Research of Chinese Medicine, International Institute for Translational Chinese Medicine, Guangzhou University of Chinese MedicineAbstract Purpose Leucine-rich repeat-containing 15 (LRRC15) is a transmembrane protein that is highly expressed in the synovium of patients with rheumatoid arthritis (RA). Brevilin A (BrA), an active compound isolated from Centipeda minima, exerts potent anti-inflammatory effects. However, the anti-RA effect of BrA and its underlying mechanism of action of BrA have not been fully elucidated. Methods Transcriptome analysis was performed to explore biomarkers of RA. An lipopolysaccharide (LPS)-induced RAW264.7 macrophage model, a TNF-α-stimulated RA fibroblast-like synoviocytes (RA-FLSs) model, as well as a collagen-induced arthritis (CIA) rat model were used to explore the anti-RA effects of BrA. Moreover, inhibition or overexpression of LRRC15 was performed to explore the role of LRRC15 signaling in the anti-RA effects of BrA. Results Transcriptome analysis of patients with RA revealed that LRRC15 expression was significantly upregulated in the synovial tissue of RA patients. BrA significantly downregulated the expression of inflammation-related markers in cell models, and inhibited their proliferation and migration; Moreover, it significantly reduced joint swelling and cartilage damage in CIA rats. Further mechanistic studies suggest that inhibition of LRRC15 inhibits cell proliferation and migration; and overexpression of LRRC15 increases the protein levels of STAT3’s downstream metastasis-related markers. Conclusions Our findings suggest that BrA, a novel LRRC15 inhibitor, has promising anti-RA activity and potently inhibits LRRC15/STAT3 signaling pathway both in vivo and in vitro. This study not only supports the development of BrA as a novel therapeutic agent for RA treatment, but also paves the way for the development of other LRRC15-targeting therapeutic strategies.https://doi.org/10.1186/s13075-025-03629-1Rheumatoid arthritisBrevilin ARheumatoid arthritis-fibroblast-like synoviocyteLRRC15STAT3 |
| spellingShingle | Zhiping Qiao Qiqi Meng Bixia Xiao Yulei Long Qi Liang Tao Su Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway Arthritis Research & Therapy Rheumatoid arthritis Brevilin A Rheumatoid arthritis-fibroblast-like synoviocyte LRRC15 STAT3 |
| title | Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway |
| title_full | Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway |
| title_fullStr | Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway |
| title_full_unstemmed | Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway |
| title_short | Brevilin A, a novel LRRC15 inhibitor, exerts potent anti-rheumatoid arthritis effects by inhibiting the LRRC15/STAT3 signaling pathway |
| title_sort | brevilin a a novel lrrc15 inhibitor exerts potent anti rheumatoid arthritis effects by inhibiting the lrrc15 stat3 signaling pathway |
| topic | Rheumatoid arthritis Brevilin A Rheumatoid arthritis-fibroblast-like synoviocyte LRRC15 STAT3 |
| url | https://doi.org/10.1186/s13075-025-03629-1 |
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