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Unraveling the changes of extracellular matrix with age and fibrotic pathology /


Extracellular matrix (ECM) is a dynamic scaffold that provides both structural support and functional integrity to various tissues and organs. By serving as a natural reservoir to a variety of resident cells, ECM actively interacts with these residing cells and regulates their behaviors ranging from differentiation and proliferation to migration and regeneration. Due to its dynamic nature, ECM constantly undergoes remodeling as the local tissues experience either physiological or pathological changes, such as aging and fibrosis. Therefore, understanding the changes occur in ECM may help the development of clinically translated stem cell applications for conditions like aging and fibrosis. In this thesis, we examine the changes that ECM undergoes with aging and pathogenesis by using two different organ systems, skeletal muscles and skin. Specifically, in the first study, we determine the biochemical changes of ECM in muscles of both wild type and dystrophic mice at various ages. We also demonstrate the structural changes of ECM associated with aging and muscle pathology. In the second study, we establish a decellularized skin model to study the effect of extracellular matrix on fibroblast behavior in an effort to understand the role of ECM on fibrosis progression. Our results show that aging and disease have a tremendous effect on biochemical composition of ECM in skeletal muscles. Also, we demonstrate that the decellularized skin model has the potential of studying the role of ECM properties on skin fibrosis, and decellularized tissue has an effect on activation of fibroblasts

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