Dynamic Expression of Genes Involved in Proteoglycan/Glycosaminoglycan Metabolism during Skin Development

Abstract

Glycosaminoglycans are important for cell signaling and therefore for proper embryonic development and adult homeostasis. Expressions of genes involved in proteoglycan/glycosaminoglycan (GAG) metabolism and of genes coding for growth factors known to bind GAGs were analyzed during skin development by microarray analysis and real time quantitative PCR. GAG related genes were organized in six categories based on their role in GAG homeostasis, viz. (1) production of precursor molecules, (2) production of core proteins, (3) synthesis of the linkage region, (4) polymerization, (5) modification, and (6) degradation of the GAG chain. In all categories highly dynamic up- and downregulations were observed during skin development, including differential expression of GAG modifying isoenzymes, core proteins, and growth factors. In two mice models, one overexpressing heparanase and one lacking C5 epimerase, differential expression of only few genes was observed. Data show that during skin development a highly dynamic and complex expression of GAG-associated genes occurs. This likely reflects quantitative and qualitative changes in GAGs/proteoglycans, including structural fine tuning, which may be correlated with growth factor handling.

Matrisomal components involved in regenerative wound healing in axolotl and Acomys: implications for biomaterial development

“…163 Moreover, it was found that sulfatase 1 is upregulated during mouse embryonic skin development and is likely involved in cellular signaling. 85 Taken together, the three enzymes that were found in the datasets regulate sulfation patterns of GAGs, which in turn modulates the bioactivity. The GAG heparan sulfate (HS) binds many proteins, such as growth factors, that reside in the ECM and the interaction of HS-binding proteins and receptors is modulated by HS proteoglycans.…”

“…Instead, the expression of genes involved in GAG biosynthesis provides information on the regulation of GAGs during biological processes. A paper published in 2018 by Uijtdewilligen et al provides a curated list of genes involved in proteoglycan/glycosaminoglycan metabolism, 85 dividing GAG-related genes into various categories based on their role in GAG homeostasis. The following four categories were selected for use in our comparison analysis: linkage region formation (8 genes), GAG chain polymerization (13 genes), GAG chain modification (32 genes), and GAG chain degradation (19 genes) (the complete gene list is available in Table S2 †).…”

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“…Due to their structure and composition, GAGs are capable of binding to many components [31][32][33][34][35][36][37] .…”