Abstract
BackgroundsCysteine-rich angiogenic inducer 61 (Cyr61) is emerging as an important regulator of tissue homeostasis and wound repair. We aim to explore the colonic mucosal expression of Cyr61 and analyze the association between Cyr61 expression and clinical course in patients with Crohn’s disease (CD).MethodsEndoscopic samples were identified from 83 CD patients with and 372 controls by searching pathological reports. Among them, age- and sex- matched 43 of each group by a propensity score were selected to compare Cyr61 expression by immunohistochemistry (IHC). IHC scores for Cyr61 expression of CD patients were divided into tertiles to evaluate the association with clinical course. We also measured the level of mRNA for Cyr 61 and proinflammatory genes in inflamed and noninflamed colonic mucosal lesions from CD patients.ResultsThe mean IHC scores for Cyr61 expression was higher in CD patients (86.5) than in controls (46.1, P < 0.001). In CD patients, the mean IHC scores for Cyr61 expression (68.3) was lower in patients with clinical recurrence than in patients without recurrence (92.2, P = 0.01). Cyr61 mRNA levels in inflamed mucosa were twofold higher than those in non-inflamed lesion (P > 0.05) and the mRNA levels of IL-6 and TLR-4 in inflamed mucosa were significantly higher than those in non-inflamed mucosa in CD patients (all P < 0.05). When CD patients were stratified into tertile groups according to IHC scores for Cyr61 expression, clinical recurrence rates tended to be lower in patients with high Cyr61 expression (P for trend = 0.02). Compared with tertile 1 of Cyr61 expression, tertile 3 of Cyr 61 expression was associated with reduced risk of clinical recurrence (OR 0.43, 95% CI 0.20–0.92) after adjustment for age, sex and CD activity index at the time of colonoscopy in CD patients (P = 0.03).ConclusionsCyr61 mucosal expression in CD patients was inversely associated with clinical course. Future study need to be considered to evaluate whether Cyr 61 may play a role in activating inflammatory responses and contributing to wound healing and tissue repair in patients with CD.
Highlights
Crohn’s disease (CD) is characterized by idiopathic chronic inflammatory damage affecting any portion of the intestinal tract [1]
Histopathologic assessment of inflammatory activities and immunohistochemistry of Cysteine-rich angiogenic inducer 61 (Cyr61) To evaluate the histopathologic assessment of inflammatory activities of biopsy specimens in patients with CD, we used the pathologic scoring system suggested by Naini et al [9] including ileitis score (0–10) and colitis score (0–17)
Cyr61 expression was analyzed in 43 patients with CD (36 with colonic tissue and 7 with ileal tissue) and 41 controls
Summary
Crohn’s disease (CD) is characterized by idiopathic chronic inflammatory damage affecting any portion of the intestinal tract [1]. Lee et al BMC Gastroenterol (2021) 21:129 these repair mechanisms may aid treatment approaches for damaged intestine in patients with CD. Cysteine-rich angiogenic inducer 61 (Cyr, CCN1) is a secreted heparin-binding extracellular matrix-associated protein and is emerging as an important regulator of tissue homeostasis and wound repair through the control of cell adhesion and cell migration [3, 4]. Lin et al suggested that serum Cyr was associated with inflammatory cytokines and disease activities in patients with rheumatoid arthritis and systemic lupus erythematosus (SLE) [7, 8]. There is limited information regarding whether Cyr plays any role in inflammatory processes or is associated with clinical disease activity and/or clinical course in patients with CD
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