ReferenceID 5314
A novel mechanism for inhibiting proliferation of rheumatoid arthritis fibroblast-like synoviocytes: geniposide suppresses HIF-1α accumulation in the hypoxic microenvironment of synovium
Inflamm Res
Objective: The excessive proliferation of fibroblast-like synoviocytes (FLSs) is a key inducement for the occurrence and development of rheumatoid arthritis (RA). Hypoxia inducible factor-α (HIF-α) accumulation is involv
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Record Fields
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- Reference Id
- 5314
- Evidence Id
- 21904
- Core Evidence Id
- 21904
- Source Reference Id
- 3882
- Herb2 Reference Id
- HBREF004679
- Subject Paper Key
- HBIN027450_36109396
- Pubmed Id
- 36109396
- Doi
- 10.1007/s00011-022-01636-5
- Paper Title
- A novel mechanism for inhibiting proliferation of rheumatoid arthritis fibroblast-like synoviocytes: geniposide suppresses HIF-1α accumulation in the hypoxic microenvironment of synovium
- Paper Abstract
- Objective: The excessive proliferation of fibroblast-like synoviocytes (FLSs) is a key inducement for the occurrence and development of rheumatoid arthritis (RA). Hypoxia inducible factor-α (HIF-α) accumulation is involved in the regulation of cell biological functions in the hypoxic microenvironment of synovium. This study aimed to investigate the roles of HIF-α and its level regulator prolyl hydroxylases (PHDs) in FLSs proliferation and to explore the regulatory effect of geniposide (GE). Materials and methods: Adjuvant arthritis rats and RA-FLSs cell line MH7A were taken as the research objects. MH7A cells were incubated in a hypoxic chamber with 2% O 2 for hypoxia treatment. CCK-8, FACS, EdU and Western blot assays were performed to evaluate MH7A cells proliferation. Iron assay was conducted to determine intracellular Fe 2+ level. Results: MH7A cells proliferation was significantly enhanced under hypoxia, accompanied by an increase of HIF-1α level. Decreased HIF-1α level by PX-478 inhibited MH7A cells proliferation. Furthermore, PHD2 was highly expressed in vivo and in vitro, and played a key role in modulation of HIF-1α protein level, which was confirmed by PHD2 inhibitor IOX4 and proteasome inhibitor MG132. GE treatment alleviated synovial hyperplasia in AA rats and inhibited MH7A cells proliferation with a reduction in HIF-1α level. Fe 2+ acts as an enzymatic cofactor to control PHD2 activity. Iron assay showed that GE reversed the decline of Fe 2+ level in MH7A cells under hypoxia. Conclusion: GE attenuates abnormal proliferation of RA-FLSs via inhibiting HIF-1α accumulation through enhancement of PHD2 activity.
- Journal
- Inflamm Res
- Publish Year
- 2022
- Experiment Subject
- rat; mh7a cells; ra-flss cell line mh7a
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Synovial Hyperplasia; Rheumatoid Arthritis; Adjuvant Arthritis
- Paper Title Cn
- Paper Title En
- A novel mechanism for inhibiting proliferation of rheumatoid arthritis fibroblast-like synoviocytes: geniposide suppresses HIF-1α accumulation in the hypoxic microenvironment of synovium
- Bilingual Status
- semi_complete