Our findings suggest that expression of apoptosis markers is related to the degree of colitis and show that apoptosis is sustained by both p53 and FasR/FasL pathways, depending on the phase of colitis development. Moreover, the lack of TG staining in typical apoptotic bodies may account for a perturbation of the cross-linked apoptotic envelope that may be an important determinant in the development of immune response in ulcerative colitis.
During an acute SARS-CoV-2 infection, a diagnosis of Aplastic Anaemia associated with Paroxysmal Nocturnal Haemoglobinuria (AA/PNH) was made in a 78-year-old woman who had presented to the emergency department with severe pancytopenia. It is possible that she had subclinical AA/PNH that was unmasked during the acute COVID-19 infection, but we can also suspect a direct role of the virus in the pathogenesis of the disease, or we can hypothesize that COVID-19 infection changed the phosphatidylinositol glycan class A (PIGA) gene pathway.
Background/Aims: Tissue transglutaminase has been reported to be involved in the healing of experimental gastric ulcer; nevertheless, other type(s) of transglutaminase could be involved. The present experiments aimed at examining whether plasma transglutaminase (factor XIIIa) contributes to such healing and at evaluating whether factor XIII supplementation improves gastric mucosal lesions. Methods: The healing effect of 200 U/kg of factor XIII administered intravenously was examined using a water immersion restraint rat model of stress gastric damage. The rats were sacrified 0, 2, 4, and 12 h after stress. The gastric mucosa was examined macroscopically and microscopically, and the transglutaminase activities were assayed in serum and gastric mucosa. Factor XIIIa and tissue transglutaminase protein levels in the gastric mucosa were analyzed by immunoblot. Immunohistochemistry was used to identify the location of tissue transglutaminase, factor XIIIa, and fibronectin in the gastric mucosa. Results: The transglutaminase activity, reduced by stress in the gastric mucosa, increased up to 12 h after stress, peaking at 4 h, when the ulcer index significantly decreased. The serum transglutaminase level was low at all time points. Exogenous administration of factor XIII allowed a faster reduction of the ulcer index that was coincident with an increased transglutaminase activity in the mucosa. Both tissue transglutaminase and factor XIIIa protein levels were reduced by 6 h of stress and increased after factor XIII administration. Immunohistochemistry showed a colocalization of both factor XIIIa and tissue transglutaminase with fibronectin in the extracellular matrix of the damaged area. Conclusions: Two forms of transglutaminase are involved in the healing of stress-induced gastric erosions, and factor XIII administration allows faster gastric mucosa healing.
A widespread from of transglutaminase, tissue transglutaminase, has been identified in a number of mammalian cell types, both normal and transformed cells; its biological role is not well understood. We investigated the effect of experimentally induced colon cancer on transglutaminase activity in the rat. Azoxymethane (15 mg/kg for six weeks), given by a course of weekly intraperitoneal injections, produces tumors almost exclusively confined to the intestinal tract. Transglutaminase activity was assayed on tissue homogenates both during the period of treatment and, when the cancer had developed, on tumor tissue and on microscopically uninjured adjacent tissue. A transient proliferative phase was present in the intestine during azoxymethane treatment: in this phase we found a coincidentally increased transglutaminase levels. Transglutaminase activity in tumors of both small and large intestine was significantly higher than in adjacent tissue. Immunohistochemistry revealed higher levels of transglutaminase in tumors, mainly localized in the extracellular matrix, than in adjacent tissues, where it was widely distributed. The present study shows that transglutaminase, besides its potential role in intracellular process during early proliferative phase of carcinogenesis, may also play an important role in matrix processing during tumor growth and differentiation.
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