Decorin Deficiency Leads to Impaired Angiogenesis in Injured Mouse Cornea

Abstract

Small leucine-rich proteoglycans play important roles in the organization of the extracellular matrix as well as for the regulation of cell behavior; two biological processes that are essential for angiogenesis. We investigated consequences of the targeted ablation of decorin (DCN), biglycan (BGN) and fibromodulin (FMOD) genes on inflammation-induced angiogenesis in the cornea. In wild-type mice, DCN was localized exclusively to the corneal stroma, while FMOD and BGN were more prominently expressed in epithelial cells. Endothelial cells from limbus blood vessels expressed BGN and FMOD, but no DCN. However, after induction of angiogenesis by chemical cauterization, DCN was expressed in the newly formed capillaries, together with BGN and FMOD. Notably, in DCN-deficient mice, the growth of vessels was significantly diminished, whereas it did not significantly change in FMOD- or BGN-deficient animals. Moreover, blood vessels of DCN-deficient mice exhibited a similar expression level of BGN as control mice, while FMOD was increased on day 3 after injury. These results indicate that DCN, in addition to its effects on fibrillogenesis, plays a regulatory role in angiogenesis and that FMOD in endothelial cells may be able to partially substitute for DCN.

Decorin is a secreted protein associated with obesity and type 2 diabetes

“…Several studies have supported a proangiogenic role for decorin and, in particular, in angiogenesis associated with inflammatory conditions. 18,[23][24][25][26] This is noteworthy as obesity has been associated with inflammation of the adipose tissue. 27 Decorin may, therefore, have a proangiogenic role during adipose tissue expansion in times of positive energy balance.…”

ADAMTS-4 and Biglycan are Expressed at High Levels and Co-Localize to Podosomes During Endothelial Cell Tubulogenesis In Vitro

“…Prominent among these are proteoglycans, such as aggrecan (Porter et al 2005) -a major structural component of cartilage (Roughley 2001). Among the proteoglycan substrates for ADAMTS members are molecules that are implicated in angiogenesis, such as versican (Cattaruzza et al 2002;Fu et al 2011;Koyama et al 2007) -a substrate for ADAMTS-1, -4, and -5 (Sandy et al 2001), decorin (Fiedler et al 2008;Järveläinen et al 1992;Schönherr et al 2004) -a substrate for ADAMTS-4 (Kashiwagi et al 2004), and biglycan (Kaji et al 2000;Schönherr et al 2004) -a substrate for ADAMTS-4 and -5 (Melching et al 2006). Although these and other studies have established an enzyme/substrate relationship between ADAMTS-1, -4, and -5 and the proteoglycans versican, decorin, and biglycan, the relationship between these two groups of molecules in the setting of vascular morphogenesis has not been fully investigated.…”

More than skin deep: connecting melanocyte pigmentation and angiogenic diseases

“…The role of FMOD and related SLRPs, including decorin and biglycan, has been explored previously under a variety of inflammatory and angiogenic conditions (6)(7)(8)(9). Somewhat surprisingly, unlike decorin-null mice, mice lacking FMOD displayed no defects in corneal angiogenesis (7); however, the work by Adini et al reveals a likely explanation for this apparently negative result (5).…”