Quantitative analysis of cadherin-11 and β-catenin signalling during proliferation of rheumatoid arthritis-derived synovial fibroblast cells

Yoshioka, Ryosuke; Kita, Yasuhiro; Nagahira, Asako; Manno, Atsushi; Makita, Naoyuki; Tomita, Urara; Murakawa, Masao

doi:10.1111/jphp.12410

Cited by 14 publications

(12 citation statements)

References 25 publications

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“…[41] The authors concluded that CDH11 is involved in IL1β-mediated pathways, and that there is an indirect interplay between the two genes via β-catenin. [41] In a related study, Chang and coworkers demonstrated that CDH11 engagement had strong synergies with IL1β signaling upon interleukin 6 (IL-6) induction in synovial fibroblasts, and that the mitogen-activated protein kinase (MAPK) [c-Jun N-terminal kinase (JNK) and extracellular signal–regulated kinase 1 and 2 (ERK1/2)] and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways were activated. [42] Thus, the signaling cascades of IL1β and CDH11 may be related through β-catenin, MAPK, and/or NF-κB in AoAFs.…”

Section: Resultsmentioning

confidence: 99%

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Attenuation of Maladaptive Responses in Aortic Adventitial Fibroblasts through Stimuli‐Triggered siRNA Release from Lipid–Polymer Nanocomplexes

et al. 2017

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Lipid-siRNA assemblies are modified with photo-responsive polymers to enable spatiotemporally-controlled silencing of interleukin 1 beta (IL1β) and cadherin 11 (CDH11), two genes that are essential drivers of maladaptive responses in human aortic adventitial fibroblasts (AoAFs). These hybrid nanocomplexes address the critical challenge of locally mitigating fibrotic actions that lead to the high rates of vascular graft failures. In particular, the lipid-polymer formulations provide potent silencing of IL1β and CDH11 that is precisely modulated by a photo-release stimulus. Moreover, a dynamic modeling framework is used to design a multi-dose siRNA regimen that sustains knockdown of both genes over clinically-relevant timescales. Multi-dose suppression illuminates a cooperative role for IL1β and CDH11 in pathogenic adventitial remodeling and is directly linked to desirable functional outcomes. Specifically, myofibroblast differentiation and cellular proliferation, two of the primary hallmarks of fibrosis, are significantly attenuated by IL1β silencing. Meanwhile, the effects of CDH11 siRNA treatment on differentiation become more pronounced at higher cell densities characteristic of constrictive adventitial remodeling in vivo. Thus, this work offers a unique formulation design for photo-responsive gene suppression in human primary cells and establishes a new dosing method to satisfy the critical need for local attenuation of fibrotic responses in the adventitium surrounding vascular grafts.

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Section: Resultsmentioning

confidence: 99%

“…[37, 41, 45] While IL1β has been widely identified as playing a key role in fibroblast proliferation, few studies have implicated CDH11. [41] For example, Vesey et al . found that IL1β was a potent inducer of proliferation with similar activities to those of TGF-β1 in human cortical fibroblasts.…”

Section: Resultsmentioning

confidence: 99%

Attenuation of Maladaptive Responses in Aortic Adventitial Fibroblasts through Stimuli‐Triggered siRNA Release from Lipid–Polymer Nanocomplexes

et al. 2017

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“…ICAM‐1 and VCAM‐1 expression plays a key role in maintaining inflammation; our study suggests that IL‐21 up‐regulates the expression of ICAM‐1 and cadherin‐11 that may partly interpret the IL‐21‐induced invasion. Cadherin‐11 mediated the β‐catenin signalling involved in IL‐1β‐induced proliferation, but was not involved in TNF‐α‐induced RA‐FLS proliferation . In this study, we found that IL‐21 induced cadherin‐11 expression in RA‐FLS; whether cadherin‐11 mediates IL‐21‐induced proliferation and invasion needs further study.…”

Section: Discussionmentioning

confidence: 61%

Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis

Xing

Jin

Sun

et al. 2016

Clinical and Experimental Immunology

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SummaryRheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial fibroblast hyperplasia and bone erosion. Fibroblast-like synoviocytes (FLS) play a pivotal role in RA pathogenesis through aggressive migration and matrix invasion, and certain proinflammatory cytokines may affect synoviocyte invasion. Whether interleukin (IL)-21 influences this process remains controversial. Here, we evaluated the potential regulatory effect of IL-21 on the migration, invasion and matrix metalloproteinase (MMP) expression in RA-FLS. We found that IL-21 promoted the migration, invasion and MMP (MMP-2, MMP-3, MMP-9, MMP-13) production in RA-FLS. Moreover, IL-21 induced activation of the phosphoinositide 3-kinase (PI3K), signal transducer and activator of transcription-3 (STAT-3) and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways, and blockage of these pathways [PI3K/protein kinase B (AKT) inhibitor LY294002, STAT-3 inhibitor STA-21 and ERK1/2 inhibitor PD98059] attenuated IL-21-induced migration and secretion of MMP-3 and MMP-9. In conclusion, our results suggest that IL-21 promotes migration and invasion of RA-FLS. Therefore, therapeutic strategies targeting IL-21 might be effective for the treatment of RA.

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“…In another study, CDH11 induced IL-6 production through MAPK signaling or NF-κB activation, and synergized with other pro-inflammatory molecules such as tumor necrosis factor-α (TNF-α) and IL-1β to enhance the expression of these inflammatory mediators [22,25]. Yoshioka et al [26] elucidated the role of CDH11 in TNF-α induced RA-FLS proliferation, which might be a β-catenin library. Moreover, Wu et al [27] found that PI3K/Akt pathway was related to the expression of CDH11 induced by pressure or inflammation, which might be involved in the pathogenesis of arthritis [9].…”

Section: Rheumatoid Arthritis (Ra) and Cdh11mentioning

confidence: 99%

Research progress in the role and mechanism of Cadherin-11 in different diseases

Chen¹,

Xiang²,

Yu³

et al. 2021

J. Cancer

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Cadherin is an important cell-cell adhesion molecule, which mediates intercellular adhesion through calcium dependent affinity interaction. Cadherin-11 (CDH11, OB-cadherin) is a member of cadherin family, and its gene is situated on chromosome 16q22.1. Increasing lines of researches have proved that CDH11 plays important roles in the occurrence and development of a lot of diseases, such as tumors, arthritis and so on. CDH11 often leads to promoter methylation inactivation, which can induce cancer cell apoptosis, suppress cell motility and invasion, and can inhibit cancer through Wnt/β-catenin, AKT/Rho A and NF-κB signaling pathways. This review focused on the current knowledge of CDH11, including its function and mechanism in different diseases. In this article, we aimed to have a more comprehensive and in-depth understanding of CDH11 and to provide new ideas for the treatment of some diseases.

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Quantitative analysis of cadherin-11 and β-catenin signalling during proliferation of rheumatoid arthritis-derived synovial fibroblast cells

Cited by 14 publications

References 25 publications

Attenuation of Maladaptive Responses in Aortic Adventitial Fibroblasts through Stimuli‐Triggered siRNA Release from Lipid–Polymer Nanocomplexes

Attenuation of Maladaptive Responses in Aortic Adventitial Fibroblasts through Stimuli‐Triggered siRNA Release from Lipid–Polymer Nanocomplexes

Interleukin-21 induces migration and invasion of fibroblast-like synoviocytes from patients with rheumatoid arthritis

Research progress in the role and mechanism of Cadherin-11 in different diseases

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