Small leucine‐rich proteoglycans exhibit unique spatiotemporal expression profiles during cardiac valve development

Abstract

Background Small Leucine Rich Proteoglycans (SLRPs) play a role in collagen fiber formation and also function as signaling molecules. Given the importance of collagen synthesis to the cardiovascular extracellular matrix (ECM), we examined the spatiotemporal expression of SLRPs, not previously investigated in the murine heart. Results Cardiac expression using antibodies specific for biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) revealed distinct patterns among the SLRPs in mesenchymal-derived tissues. DCN showed the most intense localization within the developing valve cusps, while LUM was evident primarily in the hinge region of postnatal cardiac valves. BGN, DCN and FMOD were immunolocalized to regions where cardiac valves anchor into adjacent tissues. Medial (BGN), and adventitial (BGN, DCN, FMOD and LUM) layers of the pulmonary and aortic arteries also showed intense staining of SLRPs but this spatiotemporal expression varied with developmental age. Conclusions The unique expression patterns of SLRPs suggest they have adapted to specialized roles in the cardiovascular ECM. SLRP expression patterns overlap with areas where TGFβ signaling is critical to the developing heart. Therefore we speculate that SLRPs may not only be required to facilitate collagen fiber formation but may also regulate TGFβ signaling in the murine heart.

Histone Deacetylase 3 Coordinates Deacetylase-independent Epigenetic Silencing of Transforming Growth Factor-β1 (TGF-β1) to Orchestrate Second Heart Field Development

“…We demonstrate that HDAC3 is required to maintain proper composition of both proteoglycans and collagen in the developing semilunar valves and ascending aorta. The small leucine-rich proteoglycans, such as biglycan, decorin, and fibromodulin, sequester TGF-␤ to limit its bioavailability and thereby regulate proper remodeling of the hinge region of the semilunar valves and ascending aorta (37,39). Without this sequestration, an increase of TGF-␤ bioavailability manifests as dilatation of ascending aorta, bicuspid aortic valves, and thickened semilunar valves in connective tissue disorders.…”

“…Indeed, proteoglycan deficiencies have been demonstrated in patients with these syndromes (38). Proteoglycans expressed in the developing outflow tract and semilunar valves also play a key role in the assembly of collagen fibers in the extracellular matrix (37,39). Patients with collagen deficiency, such as COL3A1 mutations in Ehlers-Danlos syndrome, show elevated TGF-␤ levels (29).…”

The small leucine-rich repeat secreted protein Asporin induces eyes in Xenopus embryos through the IGF signalling pathway

“…SLRPs have been shown to play significant roles in a number of biological events, including development, growth and the prevention of tumours (Brezillon et al, 2009;Dellett et al, 2012;Dupuis and Kern, 2014;Iozzo and Schaefer, 2010;Nikitovic et al, 2008;Shimizu-Hirota et al, 2004). Based on the amino acid sequence, ASPN is categorised with Decorin and Biglycan as a class I SLRP (Fig.…”

Molecular Functions of Glycoconjugates in Autophagy

“…The abundance of these ligands is dynamically regulated in response to different biochemical cues [150, 151]. Only recently has the pro-autophagic capacity of these ligands been recognized.…”