A potential contribution of trappin‐2 to the development of vasculopathy in systemic sclerosis

Miyagawa, Takuya; Asano, Yoshihide; Saigusa, Ryosuke; Hirabayashi, Megumi; Yamashita, Takashi; Taniguchi, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Yoshizaki, Ayumi; Miyagaki, Tomomitsu; Sato, Shinichi

doi:10.1111/jdv.15387

Cited by 8 publications

(7 citation statements)

References 52 publications

(94 reference statements)

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“…For instance, endothelial cell–specific Fli1 knockout mice spontaneously develop the histological and functional alterations characteristically seen in SSc vasculopathy, such as arteriolar stenosis, capillary dilation and increased vascular permeability 23 . Furthermore, many properties are shared by Fli1‐deficient endothelial cells and SSc endothelial cells 23‐29 . Therefore, we examined whether gene silencing of FLI1 affects VASH‐1 expression in HDMECs, but no significant change was observed (1.00 ± 0.13 [AU] versus 1.06 ± 0.05 [AU], p = 0.39; Fli1 knockdown efficiency, 82.5% [data not shown]).…”

Section: Resultsmentioning

confidence: 99%

“…However, as shown in the immunohistochemical analysis, VASH‐1 expression in dermal small vessels was comparable between SSc patients and healthy controls. Since the immunohistochemical analysis is generally semi‐quantitative, we focused on the effect of Fli1 deficiency, a key predisposing factor to induce a large part of SSc‐specific property in endothelial cells, 23‐29 on endothelial VASH‐1 expression. FLI1 siRNA did not alter the expression of VASH1 mRNA in HDMECs, further supporting our conclusion described above.…”

Section: Discussionmentioning

confidence: 99%

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Serum vasohibin‐1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis

Fukui

Nakamura

Hirabayashi

et al. 2021

Experimental Dermatology

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Vasohibin‐1 (VASH‐1) is a potent anti‐angiogenic factor mainly produced by endothelial cells. In addition, VASH‐1 prevents TGF‐β–dependent activation of renal fibroblasts. Since systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs, VASH‐1 may be involved in the development of this disease. In this study, we investigated the potential role of VASH‐1 in SSc by evaluating the clinical correlation between serum VASH‐1 levels and the expression of VASH‐1 in SSc‐involved skin. Serum VASH‐1 levels were higher in SSc patients, especially those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, SSc patients with interstitial lung disease had significantly elevated levels of serum VASH‐1 as compared to those without. Importantly, serum VASH‐1 levels correlated inversely with both the percentage of predicted vital capacity and the percentage of predicted diffusion lung capacity for carbon monoxide and positively with serum KL‐6 levels, but not serum surfactant protein D levels. In SSc‐involved skin, VASH1 mRNA was remarkably upregulated compared with healthy control skin, but the major source of VASH‐1 was not clear. Fli1 deficiency, a predisposing factor inducing SSc‐like endothelial properties, did not affect VASH‐1 expression in human dermal microvascular endothelial cells. Collectively, these results suggest that VASH‐1 upregulation in the skin and sera is linked to dermal and pulmonary fibrotic changes in SSc, while the contribution of VASH‐1 to SSc vasculopathy seems to be limited.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Serum vasohibin‐1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis

Fukui

Nakamura

Hirabayashi

et al. 2021

Experimental Dermatology

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“…However, they observed increased serum trappin-2 levels in SSc patients with digital ulcers and elevated right ventricular systolic pressure, as well as enhanced trappin-2 expression in small vessels of SSc lesional skin, suggesting that trappin-2, the precursor of elafin, plays a role in the vasculopathy in SSc. [ 15 ] Furthermore, there is substantial evidence from pre-clinical studies that indicates elafin has beneficial effects on various vascular injury and inflammation models. [ 16 ] These findings may also have implications on the role of elafin in BD, considering the role of endothelial dysfunction and vasculitis in its pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Serum Elafin as a Potential Marker of Disease Activity in Behçet's Disease

Kutlay,

Kose

2023

Indian Journal of Dermatology

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Background: Elafin is a serine protease inhibitor with anti-inflammatory properties. It is expressed in various epithelial tissues with increased production under inflammatory conditions. Increased tissue elafin expression in Behçet's disease (BD) lesions has previously been demonstrated. Aims and Objectives: We hypothesised that serum elafin might be increased in patients with BD and aimed to assess the relationship of serum elafin with disease activity and organ involvement in BD. Materials and Methods: Fifty-four BD patients (29 active, 25 inactive) and 30 healthy controls were included in this single-centre case-control study. Serum elafin was measured using ELISA. Complete blood count, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) tests were also performed. Results: Serum elafin levels were significantly higher in patients with BD (1.58 ± 0.47 ng/ml, range: 0.67–2.96) compared to controls (1.10 ± 0.28 ng/ml, range: 0.65–1.49) ( P < 0.001). Patients with active BD had higher elafin levels than patients with inactive BD ( P = 0.008). Active arthritis was associated with an increase in elafin ( P = 0.012), while the presence of mucocutaneous symptoms was not. Serum elafin correlated significantly with ESR ( P = 0.001). The ideal cut-off value for the diagnosis of BD was determined as 1.24 ng/ml with a sensitivity and specificity of 72.2% and 70.0%, respectively. Conclusion: Serum elafin is significantly increased in patients with BD. It may serve as a marker of disease activity, especially articular involvement.

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“…Recently, an epithelial host defense protein, ela n was recognized as a possible serum marker modulated in multiple pathological conditions, including brosis and vascular remodeling (3). Ela n and its precursor trappin-2 are inhibitors of human serine proteases of the chelonianin family (4).…”

Section: Introductionmentioning

confidence: 99%

“…Elgharib et al showed a statistically signi cant correlation between serum ela n levels and Psoriasis Area Severity Index (PASI) and between in ammation markers such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) (6). Furthermore, it was revealed that ela n may serve as a useful indicator of interstitial lung disease in SSc patients as well as be the biomarker of skin GvHD (3). The previous observations suggested that ela n can help in predicting transplant survival and response to treatment in acute GvHD (aGvHD) (7,8).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of elafin as a marker of skin fibrosis -a preliminary study

Polanska,

Kowalczyk,

Olewicz-Gawlik

et al. 2024

Arch Dermatol Res

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Ela n can act as a possible serum marker modulated in multiple pathological conditions, including brosis and vascular remodelling. The aim af our pilot study was to check the possible role of ela n in patients with skin brosis, including systemic sclerosis (SSc), chronic variants of graft versus host disease (cGvHD) and different variants of morphea regarding its relationship with the severity of skin involvement and clinical parameters. The study included 125 Caucasian patients and 30 healthy controls. In all groups serum ela n was measured using commercially available enzymelinked immunosorbent assay kits (Elisa). cGVHD patients presented signi cantly higher mean plasma levels of ela n in comparison to other groups of patients and there was no statistically signi cant difference in mean serum levels of ela n between morphea and SSc patients. Also there was no difference in mean serum levels of ela n in morphea patients between its clinical variants and severity of the disease, although the non-active stage morphea presented higher values of ela n concentrations. There was no correlation between ela n concentration and Rodnan skin score, lungs involvement and GFR in SSc. We noticed the elevated levels of ela n in the group of patients with cGvHD, which may suggest a relationship of this marker with a chronic disease process, including brosis. We did not nd the association of ela n and SSc as well as morphea (including severity of the disease process and phase). However, taking into account the inconsistent role of ela n in brosis, the complex regulation of the ela n gene in human keratinocytes, as well as the multifaceted involvement in skin in ammation, further studies are needed.

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A potential contribution of trappin‐2 to the development of vasculopathy in systemic sclerosis

Cited by 8 publications

References 52 publications

Serum vasohibin‐1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis

Serum vasohibin‐1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis

Serum Elafin as a Potential Marker of Disease Activity in Behçet's Disease

Evaluation of elafin as a marker of skin fibrosis -a preliminary study

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