Functions of small leucine-rich repeat proteoglycans in connective tissues

• Biological properties of connective tissues rely heavily on collagen and its use in formation of extracellular networks (matrices) in which cells can live and move. To regulate the process of collagen matrix assembly, the cells secrete small leucine-rich repeat proteoglycans (SLRPs) that bind to collagen and influence its fibril formation. In this manner, fibromodulin - one of the SLRPs - can alter intermolecular cross-linking of collagen, which has long-term implications for the structural integrity of the connective tissue. Since SLRPs can bind to collagen in via different domains, and are expressed in different tissues, their regulation of collagen matrices is fine-tuned for the physiological requirements. For example, decorin and lumican interact with collagen using their central leucine-rich repeat domains, while fibromodulin makes use of its C-terminal domain. In addition, some SLRPs can inhibit each other's binding to collagen. These differences, together with the detailed knowledge on matrix protein interactions, can be useful to explain the development of connective tissues. In a longer time perspective, this knowledge could allow to manipulate fibrotic processes in pathological conditions like cancer or atherosclerosis - the two major causes of death in our society. The potential for such intervention is high, since fibromodulin is abundant in cancer stroma, raising its interstitial fluid pressure that hinders an efficient anti-cancer drug medication. Furthermore, fibromodulin is expressed in atherosclerotic plaques, regulating the growth of the fibrous cap and activity of smooth muscle cells. These observations validate further investigations into this field of connective tissue biology.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

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