KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis
Abstract Background Rheumatoid arthritis (RA) can cause irreversible joint injury and serious disability. This study aimed to investigate how TRIM33 regulated by KLF9 affects the aggressive behaviors of synovial fibroblasts induced by tumor necrosis factor‐α (TNF‐α). Materials and Methods TNF‐α‐indu...
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| Format: | Article |
| Language: | English |
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Wiley
2022-11-01
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| Series: | Immunity, Inflammation and Disease |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/iid3.696 |
| _version_ | 1811198315521376256 |
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| author | Dan Huang Liju Tao Xiuri Du |
| author_facet | Dan Huang Liju Tao Xiuri Du |
| author_sort | Dan Huang |
| collection | DOAJ |
| description | Abstract Background Rheumatoid arthritis (RA) can cause irreversible joint injury and serious disability. This study aimed to investigate how TRIM33 regulated by KLF9 affects the aggressive behaviors of synovial fibroblasts induced by tumor necrosis factor‐α (TNF‐α). Materials and Methods TNF‐α‐induced MH7A cells were used to simulate the in vitro model of RA. TRIM33 and KLF9 expression in TNF‐α‐challenged MH7A cells and transfection efficiency were analyzed via real‐time reverse transcription polymerase chain reaction together with western blot. The viability, proliferation, invasion, and migration of TNF‐α‐induced MH7A cells after transfection was respectively detected by CCK‐8, EdU staining, transwell, and wound‐healing assays. The expression of invasion and migration‐related proteins and inflammation‐related proteins was determined by western blot and the levels of inflammatory factors were detected by enzyme‐linked immunosorbent assay. The combination between TRIM33 and KLF9 was substantiated through dual‐luciferase reporter assay and chromatin immunoprecipitation. Results TRIM33 and KLF9 expression in TNF‐α‐challenged MH7A cells was downregulated. TRIM33 elevation inhibited TNF‐α‐elicited proliferation, metastasis as well as inflammation of MH7A cells. Moreover, KLF9 was combined with TRIM33 and KLF9 promoted transcription of TRIM33. The inhibitory effect of TRIM33 overexpression on proliferation, invasion and migration and inflammation of MH7A cells induced by TNF‐α was alleviated by the downregulation of KLF9. Conclusion KLF9 positively regulates TRIM33 to suppress the abnormal MH7A cell proliferation, migration, and reduce inflammation upon exposure to TNF‐α, which was reversed by inhibiting KLF9. |
| first_indexed | 2024-04-12T01:29:20Z |
| format | Article |
| id | doaj.art-280f50082e0a44a19f85dde1ba08f95b |
| institution | Directory Open Access Journal |
| issn | 2050-4527 |
| language | English |
| last_indexed | 2024-04-12T01:29:20Z |
| publishDate | 2022-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Immunity, Inflammation and Disease |
| spelling | doaj.art-280f50082e0a44a19f85dde1ba08f95b2022-12-22T03:53:32ZengWileyImmunity, Inflammation and Disease2050-45272022-11-011011n/an/a10.1002/iid3.696KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritisDan Huang0Liju Tao1Xiuri Du2Department of Rheumatology and Immunology Affiliated Hospital of Youjiang Medical College for Nationalities Baise Guangxi Zhuang Autonomous Region ChinaDepartment of Rheumatology and Immunology Affiliated Hospital of Youjiang Medical College for Nationalities Baise Guangxi Zhuang Autonomous Region ChinaDepartment of Rheumatology and Immunology Affiliated Hospital of Youjiang Medical College for Nationalities Baise Guangxi Zhuang Autonomous Region ChinaAbstract Background Rheumatoid arthritis (RA) can cause irreversible joint injury and serious disability. This study aimed to investigate how TRIM33 regulated by KLF9 affects the aggressive behaviors of synovial fibroblasts induced by tumor necrosis factor‐α (TNF‐α). Materials and Methods TNF‐α‐induced MH7A cells were used to simulate the in vitro model of RA. TRIM33 and KLF9 expression in TNF‐α‐challenged MH7A cells and transfection efficiency were analyzed via real‐time reverse transcription polymerase chain reaction together with western blot. The viability, proliferation, invasion, and migration of TNF‐α‐induced MH7A cells after transfection was respectively detected by CCK‐8, EdU staining, transwell, and wound‐healing assays. The expression of invasion and migration‐related proteins and inflammation‐related proteins was determined by western blot and the levels of inflammatory factors were detected by enzyme‐linked immunosorbent assay. The combination between TRIM33 and KLF9 was substantiated through dual‐luciferase reporter assay and chromatin immunoprecipitation. Results TRIM33 and KLF9 expression in TNF‐α‐challenged MH7A cells was downregulated. TRIM33 elevation inhibited TNF‐α‐elicited proliferation, metastasis as well as inflammation of MH7A cells. Moreover, KLF9 was combined with TRIM33 and KLF9 promoted transcription of TRIM33. The inhibitory effect of TRIM33 overexpression on proliferation, invasion and migration and inflammation of MH7A cells induced by TNF‐α was alleviated by the downregulation of KLF9. Conclusion KLF9 positively regulates TRIM33 to suppress the abnormal MH7A cell proliferation, migration, and reduce inflammation upon exposure to TNF‐α, which was reversed by inhibiting KLF9.https://doi.org/10.1002/iid3.696KLF9rheumatoid arthritissynovial fibroblastsTRIM33 |
| spellingShingle | Dan Huang Liju Tao Xiuri Du KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis Immunity, Inflammation and Disease KLF9 rheumatoid arthritis synovial fibroblasts TRIM33 |
| title | KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis |
| title_full | KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis |
| title_fullStr | KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis |
| title_full_unstemmed | KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis |
| title_short | KLF9 positively regulates TRIM33 to inhibit abnormal synovial fibroblast proliferation, migration as well as inflammation in rheumatoid arthritis |
| title_sort | klf9 positively regulates trim33 to inhibit abnormal synovial fibroblast proliferation migration as well as inflammation in rheumatoid arthritis |
| topic | KLF9 rheumatoid arthritis synovial fibroblasts TRIM33 |
| url | https://doi.org/10.1002/iid3.696 |
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