Syndecan 1 may slow the progression of subclinical atherosclerosis in patients with ankylosing spondylitis

Yılmaz, Pınar Diydem; Kadıyoran, Cengiz; Göktepe, Mevlüt Hakan; Akkubak, Yasemin; İçli̇, Abdullah; Küçük, Adem

doi:10.1080/10641963.2022.2156529

Cited by 3 publications

(4 citation statements)

References 42 publications

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“…Among the downregulated genes were those encoding the ILs 1β, 6, 8, 18, and 33, as well as those encoding CCL7 and CCL22 (Figure 4C). Conversely, M‐M@I nanoparticles upregulated genes encoding syndecan‐1 and Hmox1, [ 54,55 ] which suppress inflammation and oxidative stress. The M‐M@I nanoparticles enriched the transcriptome in Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of “rheumatoid arthritis” and “NOD‐like receptor signaling” (Figure 4D), as well as Gene Ontology (GO) biological processes related to “inflammatory responses” (Figure 4E).…”

Section: Resultsmentioning

confidence: 99%

Ingenious Synergy of a Pathology‐Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis

Xu,

Wang,

Rong

et al. 2023

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Based on the pathological characteristics of rheumatoid arthritis, including the overproduction of reactive oxygen species (ROS), inflammatory responses, and osteoclast differentiation, a biomimetic multifunctional nanomedicine (M‐M@I) is designed. Iguratimod (IGU) is loaded, which inhibits inflammatory responses and osteoclast differentiation, into mesoporous polydopamine (MPDA), which scavenges ROS. Subsequently, the nanoparticles are coated with a cell membrane of macrophages to achieve actively targeted delivery of the nanoparticles to inflamed joints. It is shown that the M‐M@I nanoparticles are taken up well by lipopolysaccharide‐induced RAW 264.7 macrophages or bone marrow‐derived macrophages (BMDMs). In vitro, the M‐M@I nanoparticles effectively scavenge ROS, downregulate genes related to inflammation promotion and osteoclast differentiation, and reduce the proinflammatory cytokines and osteoclast‐related enzymes. They also reduce the polarization of macrophages to a pro‐inflammatory M1 phenotype and inhibit differentiation into osteoclasts. In mice with collagen‐induced arthritis, the M‐M@I nanoparticles accumulate at arthritic sites and circulate longer, significantly mitigating arthritis symptoms and bone destruction. These results suggest that the pathology‐specific biomimetic multifunctional nanoparticles are effective against rheumatoid arthritis, and they validate the approach of developing multifunctional therapies that target various pathological processes simultaneously.

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Section: Resultsmentioning

confidence: 99%

Ingenious Synergy of a Pathology‐Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis

Xu,

Wang,

Rong

et al. 2023

Small

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“…Syndecan-1 was also shown to stimulate adult neurogenesis [59]. Interestingly, higher serum syndecan-1 levels were observed in AS patients compared to healthy controls [60]. The extracellular domain of syndecan-1 can be cleaved by membrane-type matrix metalloproteinase-1 (MT1-MMP), leading to the so-called shedding that promotes cell migration [61], but shedding released into the serum could explain the elevated serum level as well.…”

Section: Discussionmentioning

confidence: 99%

Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis—With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups

Sonkodi,

Marsovszky,

Csorba

et al. 2023

IJMS

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This study aimed at analyzing the corneal neural regeneration in ankylosing spondylitis patients using in vivo corneal confocal microscopy in correlation with Langerhans cell density, morphology, and dry eye parameters. Approximately 24 ankylosing spondylitis subjects and 35 age- and gender-matched control subjects were enrolled. Data analysis showed that all corneal nerve-fiber descriptives were lower in the ankylosing spondylitis group, implicating disrupted neural regeneration. Peripheral Langerhans cell density showed a negative correlation with nerve fiber descriptions. A negative correlation between tear film break-up time and corneal nerve fiber total branch density was detected. The potential role of somatosensory terminal Piezo2 channelopathy in the pathogenesis of dry eye disease and ankylosing spondylitis is highlighted in our study, exposing the neuroimmunological link between these diseases. We hypothesized earlier that spinal neuroimmune-induced sensitization due to this somatosensory terminal primary damage could lead to Langerhans cell activation in the cornea, in association with downregulated Piezo1 channels on these cells. This activation could lead to a Th17/Treg imbalance in dry eye secondary to ankylosing spondylitis. Hence, the corneal Piezo2 channelopathy-induced impaired Piezo2-Piezo1 crosstalk could explain the disrupted neural regeneration. Moreover, the translation of our findings highlights the link between Piezo2 channelopathy-induced gateway to pathophysiology and the gateway reflex, not to mention the potential role of spinal wide dynamic range neurons in the evolution of neuropathic pain and the flare-ups in ankylosing spondylitis and dry eye disease.

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“…This disease has a subtle onset and is marked by the involvement of the sacroiliac joints, bony prominences of the spinal joints, and adjacent soft tissues, often accompanied by extra‐articular manifestations such as uveitis, inflammatory bowel disease, and psoriasis. AS significantly impacts the patient's quality of life 1–5 . In China, the incidence rate of AS is approximately 0.3%, primarily affecting young adults, with a higher prevalence among males.…”

Section: Introductionmentioning

confidence: 99%

“…AS significantly impacts the patient's quality of life. [1][2][3][4][5] In China, the incidence rate of AS is approximately 0.3%, primarily affecting young adults, with a higher prevalence among males. Various factors, including genetics, infections, environment, and immuno-inflammatory processes, have been implicated in the development of AS.…”

Section: Introductionmentioning

confidence: 99%

Mechanistic study on the improvement of immune inflammation in ankylosing spondylitis through regulation of the PI3K/AKT signaling pathway by Huangqin Qingre Chubi capsules

Cong,

Liu,

Huang

et al. 2024

Int J of Rheum Dis

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ObjectiveThis study aims to investigate the potential mechanisms by which the Hangqin Qingrechubi capsule (HQC) improves immunoinflammation in Ankylosing Spondylitis (AS).MethodsThe study combines systemic network pharmacology to predict, identify, and validate the core targets of HQC and AS. We conducted molecular docking to validate the interaction between the key active ingredients of HQC and the selected core targets associated with the PI3K/AKT signaling pathway, and employed data mining to delve deeper into the correlation between HQC usage and the improvement of clinical immunoinflammatory indicators. Additionally, AS‐PBMCs and FLS co‐culture cell models will be employed to further explore the mechanism of action of HQC in improving AS immune inflammation.ResultsBased on network pharmacology core target prediction, TNF‐α, IL‐17A, IL‐6, IL‐10, and AKT1 were identified as core targets, and KEGG enrichment analysis suggested that PI3K/AKT, IL‐17, and TNF might be key signaling pathways of HQC in improving immune inflammation in AS. The results of molecular docking demonstrated a favorable binding energy between the selected AKT1 core target and the key active components of HQC, including baicalin, baicalein, and quercetin. Clinical data mining revealed a significant correlation between HQC use and improvement in clinical immunoinflammatory indexes, such as ESR, CRP, IgA, IgM, IgG, C3, C4, patient perception scores (VAS, SAS, SDS), and (PF, SF) scores. In vitro cellular experiments further supported the significant ability of HQC to inhibit PI3K/AKT signaling pathway activation.ConclusionHQC, as an herbal compound preparation, exhibits anti‐inflammatory effects through multiple components and targets, making it a potential treatment option for AS. Furthermore, an underlying mechanism of action of HQC is its ability to ameliorate immune inflammation in AS patients by inhibiting the PI3K/AKT signaling pathway.

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Syndecan 1 may slow the progression of subclinical atherosclerosis in patients with ankylosing spondylitis

Cited by 3 publications

References 42 publications

Ingenious Synergy of a Pathology‐Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis

Ingenious Synergy of a Pathology‐Specific Biomimetic Multifunctional Nanoplatform for Targeted Therapy in Rheumatoid Arthritis

Disrupted Neural Regeneration in Dry Eye Secondary to Ankylosing Spondylitis—With a Theoretical Link between Piezo2 Channelopathy and Gateway Reflex, WDR Neurons, and Flare-Ups

Mechanistic study on the improvement of immune inflammation in ankylosing spondylitis through regulation of the PI3K/AKT signaling pathway by Huangqin Qingre Chubi capsules

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