IL13Rα1 protects against rheumatoid arthritis by combating the apoptotic resistance of fibroblast-like synoviocytes
| Autor: | Qiqi Lu, Chengfang Yao, Jihong Pan, Tianhua Xie, Tingting Feng, Luna Ge, Kehong Bi, Qingwei Guo, Guanhua Song, Lin Wang, Lei Tian, Li Qiao, Xiaomei Yang |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
lcsh:Diseases of the musculoskeletal system Synoviocyte Arthritis Apoptosis Flow cytometry Arthritis Rheumatoid IL13Rα1 Mice 03 medical and health sciences 0302 clinical medicine Western blot Synovitis medicine Animals Viability assay Rheumatoid arthritis Fibroblast Cells Cultured Cell Proliferation 030203 arthritis & rheumatology medicine.diagnostic_test business.industry Synovial Membrane Fibroblasts medicine.disease Synoviocytes 030104 developmental biology medicine.anatomical_structure Mice Inbred DBA Unfolded protein response Cancer research lcsh:RC925-935 business ER stress Research Article |
| Zdroj: | Arthritis Research & Therapy, Vol 22, Iss 1, Pp 1-10 (2020) Arthritis Research & Therapy |
| ISSN: | 1478-6362 |
| DOI: | 10.1186/s13075-020-02270-4 |
| Popis: | Background Endoplasmic reticulum (ER) stress is closely related with the pathological progression of rheumatoid arthritis (RA), and fibroblast-like synoviocytes (FLSs) are known as its resistance against ER stress-induced apoptosis. Studies on overcoming such resistance would provide a novel treatment strategy for RA in a clinical setting. Methods IL13Rα1 expression was assessed in the synovial tissue by RT-qPCR, immunohistology, and Western blot. Gain or loss of functional analysis was applied to evaluate the biological roles of IL13Rα1 in RA FLSs. Cell viability and apoptosis were assessed by MTS, Western blot, and flow cytometry. The therapeutic effects of IL13Rα1 on the severity of type II collagen-induced arthritis (CIA) in DBA-/1 mouse model were evaluated by scoring synovitis, hyperplasia, cartilage degradation, and bone destruction. Results IL13Rα1 expression was selectively downregulated when RA FLSs were stimulated by ER stress inducers. Functionally, IL13Rα1 overexpression could inhibit the viability, but induce the apoptosis of RA FLSs in the presence of ER stress inducers. Mechanistically, IL13Rα1 promotes cell apoptosis via transcriptionally activating trail expression. Besides, IL13Rα1 could interact and stabilize DR5 protein, thus forming a positive loop involving trail and DR5 to render RA FLSs more susceptible to apoptosis. Additionally, intraarticular injection of IL13Rα1 conferred therapeutic effects in CIA models and showed a limited degree of synovial proliferation and joint destruction. Conclusions Together, our data establishes a regulatory role for IL13Rα1 to combat the apoptotic resistance of RA FLSs against ER stress. The inhibitory effects of IL13Rα1 on arthritis progression suggest the therapeutic potential in RA. |
| Databáze: | OpenAIRE |
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