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Title: Action of mas Receptor in Experimentally Induced Colitis
Authors: مريم محمد علي 
Supervisor: Prof. Yunus Luqmani
Keywords: mas Receptor Colitis
Issue Date: 2015
Publisher:  Kuwait university - college of graduate studies
Abstract: iv Abstract Ang 1-7, a major component of the renin-angiotensin aldosterone system that is involved in the regulation of cardiovascular and renal functions, is thought to counteract the pro-inflammatory actions of angiotensin II and play a role in the etiology of many inflammatory diseases. In this study, we examined the effect of either exogenous administration of Ang 1-7 or inhibition of its function (by treatment with the mas receptor antagonist A779) in inflammatory bowel disease (IBD). For this we established the DSS-colitis model in balb/c mice. Physical parameters were assessed by monitoring body weight loss and colon length and thickness; colitis severity was determined macroscopically and microscopically, measuring circulating WBC in blood smear, colonic MPO activity for granulocyte infiltration and cytokine and chemokine expression in plasma by proteome array profiling. Expression/activity of key signaling molecules P-ERK1/2 and P-Akt and RAAS components including mas receptor was determined by western blotting. Ang 1-7 was measured in plasma and colon homogenate using ELISA. Severity of colitis was assessed in Ang 1-7/DSS (prophylactic and therapeutic) as well as in A-779/DSS treated groups. At 3.5% w/v dosing, DSS produced a consistent degree of colitis and was used to test the effect of Ang 1-7 in this model. All the tested parameters indicated enhanced colitis severity with increased colonic MPO activity, elevated P-ERK1/2 and P-Akt, and various cytokines and chemokines involved in chemotaxis, migration and activation of immune cells. Enhanced expression of Ang1-7 and mas receptor in the colon of DSS treated mice suggests a role of this axis in colitis development. Daily i.p injections of Ang 1-7 at doses of 0.01-0.06 mg/kg resulted in significant improvement in colitis severity at gross and histological level, and paralleled the reduced circulating levels of various cytokines and chemokines. In contrast, daily administration of the mas receptor antagonist A779 significantly worsened colitis severity through up-regulation of these mediators. Our results suggest important anti-inflammatory properties of Ang 1-7 in the pathogenesis of IBD, which may provide a future therapeutic strategy to control the disease progression.
Appears in Programs:2050 Molecular Biology

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