Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis

Lee, Beomgu; Song, You Seon; Rhodes, Christopher; Goh, Tae Sik; Roh, Jong Seong; Jeong, Hoim; Park, Jisu; Lee, Hanna; Lee, Seung-Geun; Kim, Soohyun; Kim, Mingyo; S, Lee; Robinson, William H.

doi:10.1016/j.bbrc.2019.11.112

Cited by 11 publications

(8 citation statements)

References 26 publications

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“…Having demonstrated exaggerated aldosterone-salt-induced fibrosis in TRPM7-deficient mice, we next interrogated putative Mg 2+ -sensitive signaling pathways associated with these processes especially in the heart, where effects were most pronounced. Protein phosphatase magnesium‐dependent 1A (PPM1A), a Mg 2+ dependent protein and a negative regulator of Smad3, which is associated pro-inflammatory/profibrotic pathways 31 , 32 was significantly downregulated in cardiac tissues from all treated TRPM7 +/Δkinase groups (Fig. 5a ).…”

Section: Resultsmentioning

confidence: 99%

TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

Zou

Harvey

et al. 2022

Commun Biol

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Hyperaldosteronism causes cardiovascular disease as well as hypomagnesemia. Mechanisms are ill-defined but dysregulation of TRPM7, a Mg2+-permeable channel/α-kinase, may be important. We examined the role of TRPM7 in aldosterone-dependent cardiovascular and renal injury by studying aldosterone-salt treated TRPM7-deficient (TRPM7+/Δkinase) mice. Plasma/tissue [Mg2+] and TRPM7 phosphorylation were reduced in vehicle-treated TRPM7+/Δkinase mice, effects recapitulated in aldosterone-salt-treated wild-type mice. Aldosterone-salt treatment exaggerated vascular dysfunction and amplified cardiovascular and renal fibrosis, with associated increased blood pressure in TRPM7+/Δkinase mice. Tissue expression of Mg2+-regulated phosphatases (PPM1A, PTEN) was downregulated and phosphorylation of Smad3, ERK1/2, and Stat1 was upregulated in aldosterone-salt TRPM7-deficient mice. Aldosterone-induced phosphorylation of pro-fibrotic signaling was increased in TRPM7+/Δkinase fibroblasts, effects ameliorated by Mg2+ supplementation. TRPM7 deficiency amplifies aldosterone-salt-induced cardiovascular remodeling and damage. We identify TRPM7 downregulation and associated hypomagnesemia as putative molecular mechanisms underlying deleterious cardiovascular and renal effects of hyperaldosteronism.

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Section: Resultsmentioning

confidence: 99%

TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

Zou

Harvey

et al. 2022

Commun Biol

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“…However, the precise function of PPM1A in RA progression has not been expounded. Lee et al has disclosed that PPM1A was highly expressed in RA, and PPM1A expression was positively correlated with pro-inflammatory cytokine TNF level in RA synovial fluid [ 17 ]. In this study, the data showed that PPM1A enrichment was elevated in synovial tissue from RA patients and RA-FLSs, manifesting that PPM1A might be involved in RA progression.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, miR-140-3p abundance was declined in synovial tissue and FLSs from RA patients (RA-FLSs) and from mice in arthritis models, and miR-140-3p overexpression in FLSs inhibited cell proliferation and migration [ 16 ]. Moreover, Lee et al reported that protein phosphatase magnesium-dependent 1A (PPM1A) was involved in the development of RA [ 17 ]. Nevertheless, the relationships among circMAPK9, miR-140-3p, and PPM1A in the pathogenesis of RA are undiscovered.…”

Section: Introductionmentioning

confidence: 99%

CircMAPK9 promotes the progression of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-140-3p/PPM1A axis

Luo

Chen

2021

J Orthop Surg Res

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Background Rheumatoid arthritis (RA) is a chronic inflammatory joint disease, and fibroblast-like synoviocytes (FLSs) are key effector cells in RA development. Mounting evidence indicates that circular RNAs (circRNAs) participate in the occurrence and development of RA. However, the precise mechanism of circRNA mitogen-activated protein kinase (circMAPK9) in the cell processes of FLSs has not been reported. Methods The expression levels of circMAPK9, microRNA-140-3p (miR-140-3p), and protein phosphatase magnesium-dependent 1A (PPM1A) were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot assay. Cell proliferation was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell apoptosis and cycle distribution were assessed by flow cytometry. Cell migration and invasion were tested by transwell assay. All the proteins were inspected by western blot assay. Inflammatory response was evaluated by enzyme-linked immunosorbent assay (ELISA). The interaction between miR-140-3p and circMAPK9 or PPM1A was verified by dual-luciferase reporter assay. Results CircMAPK9 and PPM1A were upregulated and miR-140-3p was downregulated in RA patients and FLSs from RA patients (RA-FLSs). CircMAPK9 silence suppressed cell proliferation, migration, invasion, inflammatory response, and promoted apoptosis in RA-FLSs. MiR-140-3p was a target of circMAPK9, and miR-140-3p downregulation attenuated the effects of circMAPK9 knockdown on cell progression and inflammatory response in RA-FLSs. PPM1A was targeted by miR-140-3p, and circMAPK9 could regulate PPM1A expression by sponging miR-140-3p. Furthermore, miR-140-3p could impede cell biological behaviors in RA-FLSs via targeting PPM1A. Conclusion CircMAPK9 knockdown might inhibit cell proliferation, migration, invasion, inflammatory response, and facilitate apoptosis in RA-FLSs via regulating miR-140-3p/PPM1A axis, offering a new mechanism for the comprehension of RA development and a new insight into the potential application of circMAPK9 in RA treatment.

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“…Third, we only measured nesfatin-1 levels in the SF of patients with RA, but not in healthy controls, because the collection of SF samples is invasive, and there are limitations to obtain SF samples from healthy controls. 46 , 47 Finally, the serum anti-CCP levels of the controls and SF anti-CCP levels of the two groups were not measured, which is considered a flaw in the study design.…”

Section: Discussionmentioning

confidence: 99%

Elevated Nesfatin-1 Level in Synovium and Synovial Fluid is Associated with Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

Zhang

Rong²,

Xu³

et al. 2021

IJGM

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Background: Adipocytokines have been proven to be involved in the progression of autoimmune diseases, including rheumatoid arthritis (RA). Nesfatin-1, a newly discovered adipokine, has recently been reported to possess potent anti-inflammatory, antiapoptotic, and antioxidative properties. However, its role in RA has not yet been reported. Therefore, this study aimed to determine nesfatin-1 levels in the synovium and synovial fluid (SF) of patients with RA and examine their correlation with clinical manifestations and proinflammatory cytokine levels. Methods: Synovium and SF samples were collected from patients with RA and non-RA patients during joint surgery. Immunohistochemistry was used to measure nesfatin-1 protein expression in the synovium. Enzyme-linked immunosorbent assay was used to measure nesfatin-1, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) levels in the synovium and SF. Pearson correlation analysis was used to evaluate the correlations between nesfatin-1 levels, RA clinical features, and proinflammatory cytokines. The diagnostic value of synovium nesfatin-1 for RA was assessed using receiver operating characteristic (ROC) curve analysis. Results: The results showed that nesfatin-1, IL-1β, and TNF-α levels in the synovium were significantly higher in patients with RA than in controls, with age and body mass index as covariates. Moreover, the results of Pearson correlation analysis showed that nesfatin-1 levels were positively correlated with IL-1β and TNF-α levels in the synovium of patients with RA. Furthermore, there was a positive relationship between synovium nesfatin-1 levels and rheumatoid factor in patients with RA. Additionally, the results of the ROC curve analysis revealed an area under the curve of 0.733 with 77.5% sensitivity and 60.0% specificity for synovium nesfatin-1 in discriminating patients with RA from controls. Conclusion: These findings suggest that increased nesfatin-1 levels in the synovium may be associated with proinflammatory cytokines and RA severity.

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Protein phosphatase magnesium-dependent 1A induces inflammation in rheumatoid arthritis

Cited by 11 publications

References 26 publications

TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

TRPM7 deficiency exacerbates cardiovascular and renal damage induced by aldosterone-salt

CircMAPK9 promotes the progression of fibroblast-like synoviocytes in rheumatoid arthritis via the miR-140-3p/PPM1A axis

Elevated Nesfatin-1 Level in Synovium and Synovial Fluid is Associated with Pro-Inflammatory Cytokines in Patients with Rheumatoid Arthritis

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