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Biochemistry of Extracellular Matrix, Varese
 
 
 
 
Research Group

Affiliations
University of Insubria
Department of Surgery & Morphological Sciences
Via Dunant, 5 - 21100 Varese - Italy
http://www4.uninsubria.it/on-line/home.html

Background and specific aims

The glycosaminoglycan (GAG) are linear sulphated polysaccharides containing uronic and hexosamine residues and, when linked to core proteins, constitute the proteoglycans. The only unsulphated GAG is hyaluronan (HA) which does not have core protein.

The synthesis of GAGs is a complex mechanism involving dozen of genes. The structural complexity of these molecules reflects their critical role in several physiological processes including pathologies outcome. Several compounds and metabolic conditions can influence the GAG synthesis. For instance, energy and UDP sugars availability deeply influence the GAG synthesis and the regulation of the enzymes involved GAG metabolism is a critical point including several epigenetic regulations.

Research projects

The specific aim of our research group is to develop the knowledge of the pathways regulating GAG synthesis in healthy conditions and pathology with particular emphasis on HA metabolism. Our project is to demonstrate that the energy status of the cells strongly influence the HA synthesis as well as the NAD/NADH ratio. Several preliminary data indicate that covalent modifications, including phosphorylation by AMPK, acetylation/deacetylation by sirtuins and O-GlcAcylation throughout activation of OGT can modulate key enzymes of the GAG metabolism. Interestingly, among these epigenetic modifications, the presence of HAS2-A1 antisense, an ncRNA, plays a critical role in several conditions, including diabetes, cancer and atherosclerosis. Our data in vitro on cell and in vivo by using mice and human specimen confirm the role of HAS2 and its antisense HAS2-AS1 in atherosclerotic plaques development.

Our preliminary data indicated that the control of gene expression of enzymes involved in the GAG synthesis are controlled by a complex network of signaling involving the phosphorylation cascade as well as the histone code. The projects involve several cell model of human pathologies including diabetes, atherosclerosis and various type of cancer that show epigenetic modifications. Another aspect explored in our group is the syndecan 4 expression in inflammation and the micro-vesicles formation in vascular cells. In this context we study also the heparansulphate chains structure. The collagen type VI expression in development is also explored as this collagen is related to the expression of HAS2 and HA synthesis in human development and in this context we use the Down syndrome disease as model for HA and type VI collagen alteration.

Facilities and equipment

Expertise:

 

Gene expression, GAG structural analysis, cell cultures, epigenetic analysis, cellular functional tests.

 

Facilities and equipments:

 

The group is equipped with most advanced technologies available, including chromatographic devices for GAG analysis (HPLC, FPLC), video imaging system, full-equipped cell culture laboratories, real time PCR, nucleofector, fluorimetric and spectrophotometric devices (plate readers), luminometer, QUELLS laser light scattering, mass spectrometer, confocal microscope with different lasers, ultra and super centrifuges, cell impedance meter.


 


Figure 1

Recent pubblications
Extracellular Matrix in Atherosclerosis: Hyaluronan and Proteoglycans Insights. - Viola M, Karousou E, D'Angelo ML, Moretto P, Caon I, De Luca G, Passi A, Vigetti D. - Curr Med Chem. 2016 Jun 6. PMID:27281127 ( 2016 )
Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation. - 2. Vigetti D, Deleonibus S, Moretto P, Bowen T, Fischer JW, Grandoch M, Oberhuber A, Love DC, Hanover JA, Cinquetti R, Karousou E, Viola M, D'Angelo ML, Hascall VC, De Luca G, Passi A. - J. Biol. Chem. 289 (42) : 28816-26. ( 2014 )
Oxidized low density lipoprotein (LDL) affects hyaluronan synthesis in human aortic smooth muscle cells. - Viola M, Bartolini B, Vigetti D, Karousou E, Moretto P, Deleonibus S, Sawamura T, Wight TN, Hascall VC, De Luca G, Passi A. - J. Biol. Chem. 288 (41) : 29595-603. ( 2013 )

 
 
 
 
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