Researchers Develop Insight into Mechanisms of Predisposition of African Americans to Fibrosis Diseases
In a recent study published in Fibrogenesis & Tissue Repair entitled “Enhanced chemokine-receptor expression, function, and signaling in healthy African American and scleroderma-patient monocytes are regulated by caveolin-1,” scientists from Medical University of South Carolina reported new insights into the mechanism of predisposition to lung and skin fibrosis in African American subgroups.
Fibrosis relies on accumulation of excess fibrous like collagen in an organ or tissue due to a reactive/reparative process. The latter is similar to scarring in response to injury. Numerous organs/body parts can be affected by fibrosis and examples include skin, lung and liver. Patients with fibrosis may suffer from diverse symptoms, depending on the organ that is affected and progression stage of the disease. For example, while patients with pulmonary fibrosis suffer from shortness of breath, skin fibrosis (systemic sclerosis) yields itchy and reddish skin with visible blood vessels. The process of fibrosis consists physiologically of depositing connective tissue that yields changes in architecture and function of the organ/tissue. With respect to social constructs, it is known that African American have predisposition toward fibrotic diseases of the skin, lung, and other organs compared to Caucasians. However, little is known about the molecules that are responsible as well as their mechanism of action. The study carried out recently at Medical University of South Carolina, shed new light on these mechanisms.
In this study, a large number of patients with verified fibrosis disease donated blood samples. In addition, demographic data for patients and healthy control donors were also included. Blood analysis and cell isolation, essays and imaging were carried out using standard analytic methods. The data were verified and validated on mice models treated with th anticancer drug bleomycin, then all data was statistically analyzed. The results illustrated that the receptors of signaling molecules released by white blood cells capable of affecting the behavior of other cells (called chemokine) are present in high levels in white blood cells of healthy African Americans when compared to healthy Caucasians, and further increased in patients suffering from skin fibrosis (systemic sclerosis). Moreover, it is found that the cells bearing chemokine receptors accumulate substantially in fibrotic lung and skin tissue of patients with systemic sclerosis as well as in mice treated with bleomycin. By contrast, this accumulation decreased in mice treated with caveolin-1 scaffolding domain peptide, sort of tumor suppressor gene.
In summary, the data suggest that white blood cells (monocytes) and cells derived from monocytes (fibrocytes) play a key role in lung and skin fibrosis as well as predisposition of African American to fibrotic diseases. These findings demonstrate that chemokine receptors and signaling molecules particularly caveolin-1 are important targets for developing treatments for fibrotic diseases in the future.