Expression of apoptotic and proliferation factors in gastric mucosa of patients with systemic sclerosis correlates with form of the disease

Abstract

Despite high prevalence of patients with gastric disease in systemic sclerosis (SSc), its pathogenesis is still poorly understood. We immunohistochemically analysed biopsies of gastric mucosa (GM) in 5 controls and 15 patients with different forms of SSc: limited cutaneous (lc), diffuse cutaneous moderate (sys1) and severe (sys2). The number of positive cells was analysed by a Kruskall-Wallis test, P < 0.05 was considered statistically significant. Percentage of proliferating (Ki-67 positive) cells was highest in sys1 (3% in superficial and 4,6% in deeper parts of GM), which dropped to 1% in sys2. Percentage of α-smooth muscle actin (α-SMA) positive cells was 5% in controls, 9% in superficial GM, while in deeper GM rose from 7% to 19% in sys1 and sys2, thus indicating increased myofibroblast population. Caspase-3 positive apoptotic cells characterized 1,5–2% of controls, 8% of superficial and 6% of deeper GM cells in sys1. In sys2, apoptosis affected 50% of surface epithelial and gland cells and 30% of deeper glands, and correlated with increased fibrosis and decreased syndecan-1 expression. Our data demonstrate that sys1 is the most „active” proliferating form of SSc. Sys2 characterize collagen deposition, surface epithelium defects, extensive apoptosis and low proliferation, GM atrophy and loss of function.

Connexin 37, 40, 43 and Pannexin 1 Expression in the Gastric Mucosa of Patients with Systemic Sclerosis

“…In lcSSc and dsSSc samples, histological changes included hyalinization of the lamina propria, defects of the surface epithelium, and lymphocyte accumulations (a more detailed description can be found in our previous study [ 27 ]).…”

“…While many advances in understanding the pathogenesis of fibrosis in SSc have been made, the interaction and involvement of different pathways leading to its appearance are still not fully determined. Multiple studies have demonstrated morphological changes consistent with fibrosis, such as collagen deposition, myofibroblast accumulation, and immune cell infiltration in the gastric mucosa of SSc patients [ 27 , 29 , 30 ]. Increased proliferation and apoptosis of both epithelial and lamina propria cells have also been described [ 27 ], as well as changes in fibrosis-associated signaling pathways in other parts of the gastrointestinal tract [ 31 , 32 ].…”

“…Multiple studies have demonstrated morphological changes consistent with fibrosis, such as collagen deposition, myofibroblast accumulation, and immune cell infiltration in the gastric mucosa of SSc patients [ 27 , 29 , 30 ]. Increased proliferation and apoptosis of both epithelial and lamina propria cells have also been described [ 27 ], as well as changes in fibrosis-associated signaling pathways in other parts of the gastrointestinal tract [ 31 , 32 ]. The morphological characteristics and histological differences of our samples, which were described in our previous study [ 27 ], are in line with the changes reported in other studies [ 29 , 30 ].…”

“…The tissue samples were gathered as previously described [ 27 ]. Biopsies of the gastric mucosa were collected from each patient using upper gastrointestinal endoscopy.…”

Novel approach for quantification of multiple immunofluorescent signals using histograms and 2D plot profiling of whole-section panoramic images

“…In this approach, there is no need for selection of multiple ROIs because panoramic images are analyzed entirely. The selection of ROIs prior to actual quantification of IF signals of IHC staining is the usual procedure in many semi-quantitiative and quantitative scoring systems 15 – 19 . While this may be sufficient when analyzing particular structures or expression of highly specific markers, it may not be adequate for quantification of ubiquitously expressed markers whose expression domains cannot be covered by several ROIs on high magnification (Fig.…”