Biochemistry of the extracellular matrix

Group
Glycosaminoglycans (GAGs) are sulfur-containing unbranched polysaccharides containing uronic and hexosamines which, when bound to a protein core, constitute proteoglycans. The only GAG that is not sulfur and not bound to a protein core is hyaluronic acid (HA). GAG synthesis is a complex mechanism involving dozens of genes and the structural complexity of GAGs reflects their biological importance. In fact, GAGs can interact with many molecules playing a fundamental role in many physiological processes and in the onset of diseases. The specific purpose of the group is the development of knowledge of the ways of synthesis of GAGs in health conditions and in pathology, with particular attention to the study of hyaluronic acid. Our intention is to demonstrate that the energy conditions of the cell, the energy charge as well as the NAD / NADH ratio, deeply influence the metabolism of hyaluronic acid. Furthermore, our studies also show that covalent modifications modulate both the enzymatic activity and the gene expression of key enzymes of the synthetic hyaluronic acid pathways (HASs, hyaluronan synthasis). Among these modifications are the phosphorylations due to AMPK, sirtuin-dependent acetylations and deacetylations, O-glucnacylation due to the activation of OGT. We have discovered that there is an antisense RNA of HAS2 (HAS2-AS1), a long non coding RNA, which plays a critical role in epigenetically regulating the expression of HAS2 in various pathological conditions such as diabetes, cancer and arteriosclerosis. From our data it is evident that a complex network of molecular controls regulates the synthesis of GAGs involving the phosphorylation cascade and the histone code. In vascular cells we also study the expression of heparan sulfate proteoglycans, in particular syndecane-4, characterizing the expression of the protein core and the structure of the GAG. Both of these GAGs, hyaluronic acid and heparan sulfate, have an important role in the bioavailability and metabolism of lipoproteins, in particular those rich in cholesterol (LDL), revealing an increasing importance in the development of vascular pathologies.
date/time interval:
(January 1, 2020 - )

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Overview

Glycosaminoglycans (GAGs) are sulfur-containing unbranched polysaccharides containing uronic and hexosamines which, when bound to a protein core, constitute proteoglycans. The only GAG that is not sulfur and not bound to a protein core is hyaluronic acid (HA). GAG synthesis is a complex mechanism involving dozens of genes and the structural complexity of GAGs reflects their biological importance. In fact, GAGs can interact with many molecules playing a fundamental role in many physiological processes and in the onset of diseases. The specific purpose of the group is the development of knowledge of the ways of synthesis of GAGs in health conditions and in pathology, with particular attention to the study of hyaluronic acid. Our intention is to demonstrate that the energy conditions of the cell, the energy charge as well as the NAD / NADH ratio, deeply influence the metabolism of hyaluronic acid. Furthermore, our studies also show that covalent modifications modulate both the enzymatic activity and the gene expression of key enzymes of the synthetic hyaluronic acid pathways (HASs, hyaluronan synthasis). Among these modifications are the phosphorylations due to AMPK, sirtuin-dependent acetylations and deacetylations, O-glucnacylation due to the activation of OGT. We have discovered that there is an antisense RNA of HAS2 (HAS2-AS1), a long non coding RNA, which plays a critical role in epigenetically regulating the expression of HAS2 in various pathological conditions such as diabetes, cancer and arteriosclerosis. From our data it is evident that a complex network of molecular controls regulates the synthesis of GAGs involving the phosphorylation cascade and the histone code. In vascular cells we also study the expression of heparan sulfate proteoglycans, in particular syndecane-4, characterizing the expression of the protein core and the structure of the GAG. Both of these GAGs, hyaluronic acid and heparan sulfate, have an important role in the bioavailability and metabolism of lipoproteins, in particular those rich in cholesterol (LDL), revealing an increasing importance in the development of vascular pathologies.
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