A potential contribution of psoriasin to vascular and epithelial abnormalities and inflammation in systemic sclerosis

Takahashi, Takehiro; Asano, Yoshihide; Yamashita, Takashi; Nakamura, Kouki; Saigusa, Ryosuke; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Hirabayashi, Megumi; Taniguchi, Takashi; Yoshizaki, Ayumi; Sato, Shinichi

doi:10.1111/jdv.14459

Cited by 10 publications

(12 citation statements)

References 31 publications

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“…The significance of psoriasin was emphasized by Awad et al demonstrating an association of psoriasin levels with intima-media thickness of patients and indicating a potential link between psoriasis and atherosclerosis [41]. In addition, higher serum levels of psoriasin were also found in patients with systemic sclerosis [42]. A previous study of S100A7, S100A8, S100A9, and S100A12 showed that all these alarmins were significantly higher in psoriatic patients than in controls.…”

Section: Discussionmentioning

confidence: 98%

Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris

Borský

Fiala

Andrýs

et al. 2020

Mediators of Inflammation

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Background. Psoriasis vulgaris is a chronic autoimmune disease associated with systemic inflammation. Increased levels of numerous cytokines, chemokines, growth factors, and other molecules were found in the skin and in the circulation of psoriatic patients. Alarmins, also known as danger signals, are intracellular proteins, which are released to an extracellular space after infection or damage. They are the markers of cell destructive processes. Objective. The aim of the present study was to evaluate the suitability of selected alarmins (HMGB1, IL-33, S100A7, and S100A12) as potential biomarkers of severity of psoriasis and to explore possible relationships between these proteins for the purpose of better understanding their roles in the immunopathology of psoriasis. Methods. The serum levels of selected alarmins were measured in 63 psoriatic patients and 95 control individuals. The levels were assessed by the ELISA technique using commercial kits. The data were statistically processed with MedCalc version 19.0.5. Results. In psoriatic patients, we found significantly increased levels of HMGB1 (p<0.05), IL-33 (p<0.01), S100A7 (p<0.0001), and S100A12 (p<0.0001). In addition, we found a significant relationship between HMGB1 and S100A7 (Spearman’s rho=0.276, p<0.05) in the patients and significant relationship between HMGB1 and IL-33 in the controls (Spearman’s rho=0.416, p<0.05). We did not find any relationship between observed alarmins and the disease severity. Conclusions. The alarmins HMGB1, IL-33, S100A7, and S100A12 were significantly elevated in the serum of patients, which states the hypothesis that they play specific roles in the immunopathology of psoriasis. However, we have not yet found a relationship between observed alarmins and the disease severity. The discovery of the relationship between HMGB1 and S100A7 is a novelty that should be studied in the future to further clarify its role and importance.

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Section: Discussionmentioning

confidence: 98%

Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris

Borský

Fiala

Andrýs

et al. 2020

Mediators of Inflammation

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“…Over three decades, several studies have demonstrated the upregulation of disease-associated molecules in the epidermis of SSc-involved skin, such as endothelin-1, TGF-β, CCL2, vascular endothelial growth factor, IL-21 receptor, wound healing-associated cytokeratins (keratin 6 and keratin 16), IL-1α, CTGF, IL-6, TNF-α, CCL5, psoriasin and galectin-7 [ 112 , 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 ]. Considering the potent pro-fibrotic effect of IL-1α, CTGF and IL-6, SSc keratinocytes likely contribute to the activation of dermal fibroblasts.…”

Section: The Additional Organ-specific Pathologiesmentioning

confidence: 99%

The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies

Asano

2020

JCM

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Systemic sclerosis (SSc) is a multisystem autoimmune and vascular disease resulting in fibrosis of various organs with unknown etiology. Accumulating evidence suggests that a common pathologic cascade across multiple organs and additional organ-specific pathologies underpin SSc development. The common pathologic cascade starts with vascular injury due to autoimmune attacks and unknown environmental factors. After that, dysregulated angiogenesis and defective vasculogenesis promote vascular structural abnormalities, such as capillary loss and arteriolar stenosis, while aberrantly activated endothelial cells facilitate the infiltration of circulating immune cells into perivascular areas of various organs. Arteriolar stenosis directly causes pulmonary arterial hypertension, scleroderma renal crisis and digital ulcers. Chronic inflammation persistently activates interstitial fibroblasts, leading to the irreversible fibrosis of multiple organs. The common pathologic cascade interacts with a variety of modifying factors in each organ, such as keratinocytes and adipocytes in the skin, esophageal stratified squamous epithelia and myenteric nerve system in gastrointestinal tract, vasospasm of arterioles in the heart and kidney, and microaspiration of gastric content in the lung. To better understand SSc pathogenesis and develop new disease-modifying therapies, it is quite important to understand the complex pathogenesis of SSc from the two distinct perspectives, namely the common pathologic cascade and additional organ-specific pathologies.

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“…[ ] Altered expression of wound healing‐associated molecules and partially evoked epithelial‐mesenchymal transition are also noted in SSc keratinocytes. [ ] Another important observation is that epithelial cell‐specific Fli1 knockout mice, whose epithelial cells reproduce an SSc‐like property, spontaneously develop dermal and oesophageal fibrosis at least partially due to the activation of dermal and oesophageal stratified epithelia. [ ] Therefore, further studies with epithelial cells would provide us with a useful clue to better understand the complicated disease process of SSc.…”

Section: Introductionmentioning

confidence: 99%

A potential contribution of decreased galectin‐7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis

Saigusa

Yamashita

Miura

et al. 2019

Experimental Dermatology

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Backgrounds Stratified epithelia have caught much attention as potential contributors to the development of dermal and oesophageal fibrosis in systemic sclerosis (SSc). Galectin‐7 is a marker of all types of stratified epithelia, which is involved in the maintenance of epidermal homeostasis. So far, the role of galectin‐7 has not been studied in SSc. Objectives To investigate the potential contribution of galectin‐7 to the development of clinical manifestations in SSc. Methods Galectin‐7 expression was examined in skin samples and cultured keratinocytes by immunostaining and/or quantitative reverse transcription PCR. Serum galectin‐7 levels were determined by enzyme‐linked immunosorbent assay in 63 SSc and 20 healthy subjects. Results Galectin‐7 expression was markedly decreased in the epidermis of SSc lesional skin compared with that of healthy control skin. Serum galectin‐7 levels were significantly lower in SSc patients than in healthy controls and inversely correlated with skin score. In addition, SSc patients with diffuse pigmentation and those with oesophageal dysfunction had significantly decreased serum galectin‐7 levels as compared to those without each symptom. Importantly, endothelin‐1 stimulation suppressed galectin‐7 expression in normal human keratinocytes, and bosentan, a dual endothelin receptor antagonist, reversed circulating galectin‐7 levels and epidermal galectin‐7 expression in SSc patients. Conclusions Galectin‐7 downregulation in stratified epithelia, which is mediated at least partially by autocrine endothelin stimulation, may contribute to the development of cutaneous manifestations and oesophageal dysfunction in SSc patients.

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A potential contribution of psoriasin to vascular and epithelial abnormalities and inflammation in systemic sclerosis

Abstract: Our findings indicate a possible contribution of psoriasin to the development of clinical symptoms associated with vascular and epithelial abnormalities and inflammation in SSc, further supporting the roles of antimicrobial peptides in the SSc pathogenesis.

Cited by 10 publications

References 31 publications

Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris

Alarmins HMGB1, IL-33, S100A7, and S100A12 in Psoriasis Vulgaris

The Pathogenesis of Systemic Sclerosis: An Understanding Based on a Common Pathologic Cascade across Multiple Organs and Additional Organ-Specific Pathologies

A potential contribution of decreased galectin‐7 expression in stratified epithelia to the development of cutaneous and oesophageal manifestations in systemic sclerosis

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