Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions

Abstract

BackgroundIn this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF).ResultsBAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV.ConclusionsThe results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.

Myenteric Denervation Downregulates Galectin-1 and -3 Expression in Gastric Carcinogenesis

“…Using the same materials, we recently observed a significant increase in mast cell number, particularly in denervated stomachs (group IV), that was associated with the development of the lesions in the gastric antrum [8]. Further, phenotypic changes in mast cell heterogeneity from mucosal (MMCs) to connective tissue mast cell (CTMCs) correlated with myenteric denervation [8], suggesting a protective effect of denervation against the development of tumors through the release of anti-tumor mediators, such as cytokines (IL-2, IL-21 and TNF) and heparin [14].…”

“…Further, phenotypic changes in mast cell heterogeneity from mucosal (MMCs) to connective tissue mast cell (CTMCs) correlated with myenteric denervation [8], suggesting a protective effect of denervation against the development of tumors through the release of anti-tumor mediators, such as cytokines (IL-2, IL-21 and TNF) and heparin [14]. In denervated stomachs with lesions (group IV), the tumor stroma showed the most robust inflammatory influx compared with nondenervated stomachs (group III), particularly into malignant epithelial lesions.…”

“…Increased mast cell density has been described in several types of cancer [6], including gastric carcinomas [7,8]. In gastric adenocarcinomas, the release of mast cell mediators is associated with changes in the microvascular basal lamina that mediate the blood vessel remodeling [9,10].…”

Cell Reactions in Gastric Tube and Colon Transplants in Stenoses of Esophageal Anastomosis

“…Sclerogenesis in the gastric tube transplant was often associated with hyperplasia and hypertrophy of the smooth muscle cells and elastic fi bers [1]. This hyperplasia of fi brillary structures to a certain extent can be caused by denervation of the stomach [8] performed at the stage of transplant formation and mobilization. Stimulation of biosynthetic reaction of leiomyocytes in the gastric tube potentially aggravating sclerosis is also worthy of note.…”

Formas digestivas da doença de Chagas e carcinogênese: um estudo de associação

“…Cada um desses tipos celulares podem ser encontrados em íntima associação com elementos do SNE, fibras nervosas vagais e nervos sensoriais espinais 10 e cooperam com o SNE estabelecendo a primeira linha de defesa contra a invasão de antígenos. Todas as células imunológicas são fontes potentes de sinais parácrinos para o SNE, a exemplo dos mastócitos, que armazenam mediadores farmacológicos em seus grânulos implicados na resposta a estímulos imunológicos potencialmente prejudiciais à integridade do trato gastrintestinal, incluindo proteínas com atividades antitumorais 17 .…”