Roles of autophagy in rheumatoid arthritis

Ding, Jinhui; Hong, Fen-Fang; Yang, Shaoyu

doi:10.55563/clinexprheumatol/exg1ic

Cited by 6 publications

(2 citation statements)

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“…Dysfunctional autophagy is associated with the development of RA. 20 Here, we found that oxidative stress inhibited mitochondrial autophagy in RA-FLS. Studies have shown that acute dissipation of mitochondrial membrane potential by mitochondrial uncouplers (FCCP) can initiate mitophagy.…”

Section: Discussionmentioning

confidence: 64%

PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in H2O2-Induced Abnormal Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

Wang¹,

Chen²,

Shao³

et al. 2023

JIR

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Introduction To explore the role of PINK1/Parkin-mediated mitochondrial autophagy in H 2 O 2 -induced abnormal proliferation of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS). Methods Firstly, we isolated fibroblast like synoviocytes (RA-FLS) from RA patients. H 2 O 2 -induced oxidative stress, and NAC (a ROS inhibitor) or FCCP (a mitochondrial autophagy activator) treatment inhibited ROS level or activate mitochondrial autophagy in RA-FLS. MitoSOX Red, JC-1 kit, DCFH-DA kit and CCK8 kit were used to evaluate mitochondrial redox status, mitochondrial membrane potential, intracellular ROS level and cell activity, respectively. Western blot was used to detect the protein expression. The rat model of Freund’s complete adjuvant arthritis (AA) was established and treated with NAC and FCCP, respectively. The pathological changes of synovium and the percentage of apoptotic cells in synovium were detected by H&E and TUNEL staining, respectively. Results We have successfully isolated synovial cells from RA patients. Using 5μM H 2 O 2 to stimulate RA-FLS could induce mitochondrial abnormalities of RA-FLS and inhibit RA-FLS autophagy. FCCP could reverse the effect of H 2 O 2 on RA-FLS cell proliferation and apoptosis. NAC could reverse the effect of H 2 O 2 on PINK1/Parkin. Overexpression of PINK1 or Parkin reversed the effect of H 2 O 2 on RA-FLS mitochondrial autophagy, proliferation and apoptosis. The in vivo experiment results showed that both NAC and FCCP could prevent the pathogenesis of RA, reduce RA-FLS cell viability and increase RA-FLS cell apoptosis. Conclusion The PINK1/Parkin-mediated mitochondrial autophagy participates in H 2 O 2 -induced abnormal proliferation of RA-FLS, and targeting of PINK1/Parkin-mediated mitochondrial autophagy may be the key mechanism in the treatment of RA.

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Section: Discussionmentioning

confidence: 64%

PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in H2O2-Induced Abnormal Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

Wang¹,

Chen²,

Shao³

et al. 2023

JIR

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“…Autophagy dysregulation has been implicated in several autoimmune diseases, including RA. Enhanced autophagy contributes to RA FLS hyperplasia and apoptosis resistance, production of citrullinated peptides, osteoclastogenesis and bone resorption, resulting in severe bone and cartilage damage [66]. The co-administration of 1 and diclofenac has been routinely used in Chinese medicine for the treatment of RA.…”

Section: Pentacyclic Triterpenesmentioning

confidence: 99%

Triterpenes as Potential Drug Candidates for Rheumatoid Arthritis Treatment

Faustino

Pinheiro

Duarte

2023

Life

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Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by joint inflammation, swelling and pain. Although RA mainly affects the joints, the disease can also have systemic implications. The presence of autoantibodies, such as anti-cyclic citrullinated peptide antibodies and rheumatoid factors, is a hallmark of the disease. RA is a significant cause of disability worldwide associated with advancing age, genetic predisposition, infectious agents, obesity and smoking, among other risk factors. Currently, RA treatment depends on anti-inflammatory and disease-modifying anti-rheumatic drugs intended to reduce joint inflammation and chronic pain, preventing or slowing down joint damage and disease progression. However, these drugs are associated with severe side effects upon long-term use, including immunosuppression and development of opportunistic infections. Natural products, namely triterpenes with anti-inflammatory properties, have shown relevant anti-arthritic activity in several animal models of RA without undesirable side effects. Therefore, this review covers the recent studies (2017–2022) on triterpenes as safe and promising drug candidates for the treatment of RA. These bioactive compounds were able to produce a reduction in several RA activity indices and immunological markers. Celastrol, betulinic acid, nimbolide and some ginsenosides stand out as the most relevant drug candidates for RA treatment.

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Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics

Zeng,

Yu,

Yang

et al. 2024

Sci Rep

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To explore the molecular network mechanism of Celastrol in the treatment of rheumatoid arthritis (RA) based on a novel strategy (integrated systems pharmacology, proteomics, transcriptomics and single-cell transcriptomics). Firstly, the potential targets of Celastrol and RA genes were predicted through the database, and the Celastrol-RA targets were obtained by taking the intersection. Then, transcriptomic data and proteomic data of Celastrol treatment of RA were collected. Subsequently, Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were imported into Metascape for enrichment analysis, and related networks were constructed. Finally, the core targets of Celastrol-RA targets, differentially expressed genes, and differentially expressed proteins were mapped to synoviocytes of RA mice to find potential cell populations for Celastrol therapy. A total of 195 Celastrol-RA targets, 2068 differential genes, 294 differential proteins were obtained. The results of enrichment analysis showed that these targets, genes and proteins were mainly related to extracellular matrix organization, TGF-β signaling pathway, etc. The results of single cell sequencing showed that the main clusters of these targets, genes, and proteins could be mapped to RA synovial cells. For example, Mmp9 was mainly distributed in Hematopoietic cells, especially in Ptprn+fibroblast. The results of molecular docking also suggested that Celastrol could stably combine with molecules predicted by network pharmacology. In conclusion, this study used systems pharmacology, transcriptomics, proteomics, single-cell transcriptomics to reveal that Celastrol may regulate the PI3K/AKT signaling pathway by regulating key targets such as TNF and IL6, and then play an immune regulatory role.

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Roles of autophagy in rheumatoid arthritis

Cited by 6 publications

References 0 publications

PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in H2O2-Induced Abnormal Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

PINK1/Parkin-Mediated Mitochondrial Autophagy Participates in H2O2-Induced Abnormal Proliferation of Fibroblast-Like Synoviocytes in Rheumatoid Arthritis

Triterpenes as Potential Drug Candidates for Rheumatoid Arthritis Treatment

Exploring the mechanism of Celastrol in the treatment of rheumatoid arthritis based on systems pharmacology and multi-omics

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