The natural history of diverticular disease (DD) is poorly known. Most accredited patho-mechanisms refer to the remodeling of tunica muscularis with fibrosis and loss of colonic compliance. The contribution of oxidative stress begins to be considered.
Main purpose of the project is the advancement of knowledge in the pathophysiology of DD by focusing on the pathogenic role of gender-related oxidative stress.
Recent studies have demonstrated that pre-menopausal woman is protected by the insurgence of complicated DD thank to the contribution of estrogens. These ovarian hormones display beneficial effect able to prevent proliferative, fibrotic and oxidative imbalance. Furthermore, they also positively influence the abundance of mitochondrial DNA and mitochondrial functions.
To improve the knowledge of the specific gender-related oxidative neuromuscular alterations involved in DD, we will perform detailed analysis on human colonic specimens obtained from patients with different stage of disease (i.e . patients undergoing surgery for complicated DD; patients with asymptomatic diverticulosis; patients without diverticula). Analysis will be conducted separately on circular and longitudinal muscle layer.
The oxidative status, the mitochondrial respiratory chain function and biogenesis, collagen imbalance and phenotype will be evaluated on tissue and isolated single cells. Different practical methodology based on immunohistochemistry, biochemical and molecular biology will be utilized, to identify biomarkers and alterations involved.
Main strengths of this project is the systematic methodological approach consistent in the evaluation of homogenous group of patients with different clinical expression of DD. The further advantage is the accuracy placed in studying simultaneously the circular and longitudinal smooth muscle layers of the same patients.
The results will be of great help to pursue tailored-therapeutic algorithm strategies.
