AEBP1/ACLP'nin Protein Etklileşim Ağının Proteomik ve Biyoinformatik Yöntemlerle Araştırılması

Abstract

Extracellular Matrix (ECM) is the mechanical supportive structure for cells and tissues. Chronic damage may cause loss of ECM integrity that may result in fibrosis which is the progressive and irreversible accumulation of ECM proteins such as collagens. Fibrosis leads to loss of function in tissues and organs where it may develop likewise the skeletal muscle. Understanding the key regulators of this process may help to stop the progressive detorioration. Mutations in the Adipocyte Enhencer Binding Protein 1 / Aortic Carboxypeptidase Like Protein (AEBP1/ACLP) gene have been associated with Ehlers-Danlos Syndrome, characterized with increased elasticity in connective tissues that are vulnerable to physical damage. These findings point to the fact that AEBP1/ACLP may contribute to collagen organization. AEBP1/ACLP was observed to be upregulated in differentiation and fibrosis in the skeletal muscle along with ECM synthesis and organization. Thus it has been hypothesized that AEBP1/ACLP might be a mediator of fibrosis and ECM maturation process. Yet, neither the function nor the protein partners for AEBP1/ACLP has been defined. Identification of protein-protein interactions using high throughput technologies of a protein helps to understand it’s unknown function. In order to conduct such high-throughput proteomics analyses, proximity proteomics tools are developed and validated in this thesis work. Furthermore, AEBP1/ACLP expression was analyzed in transcriptome and proteom studies conducted in various skeletal muscle sample sets. Thses analyzes were directed to dissect out alterations in matrisome proteins in both in vivo and in vitro conditions. Differentially expressed common gene sets were identified in different cell and tissue types modeling regeneration and differentiation that pinpointed alterations of matrisome proteins.