Vascular Calcification - Pathological Mechanism and Clinical Application - . Extracellular matrix tenascin-X in calcific aortic valves
Matsumoto, K.-i.
Clinical Calcium 25(5): 701-710
2015
ISSN/ISBN: 0917-5857 PMID: 25926574 Document Number: 683454
We previously disclosed a novel extracellular matrix tenascin-X (TNX) , the largest member of the tenascin family. So far, we have made efforts to elucidate the roles of TNX. TNX is involved in collagen deposition, collagen fibrillogenesis, and modulation of collagen stiffness. Homozygous mutations in TNXB, the gene encoding TNX, cause a classic-type Ehlers-Danlos syndrome (EDS) , a heritable connective tissue disorder, whereas haploinsufficiency of TNXB and heterozygous mutations in TNXB are associated with hypermobility-type EDS. Recently, we performed proteomic analyses of calcific aortic valves (CAVs) compared with relatively adjacent normal tissues to understand the underlying molecular mechanisms of dystrophic valvular calcification. Interestingly, we found that TNX was the protein with the greatest decrease in expression among the differentially expressed proteins and that expression levels of proteins modulating collagen structure and function, such as type I collagen and decorin, were also decreased in CAVs. In this review, I will discuss about the decreased level of collagen due to the reduction of expression levels of proteins that play regulatory roles in collagen functions such as fibril organization and fibrillogenesis in CAVs.