Glycosaminoglycans: a link between development and regeneration in the lung: a link between development and regeneration in the lung

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Abstract

What can we learn from embryogenesis to increase our understanding of how regeneration of damaged adult lung tissue could be induced in serious lung diseases such as chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF) and asthma? The local tissue niche determines events in both embryogenesis and repair of the adult lung. Important constituents of the niche are extracellular matrix (ECM) molecules including proteoglycans and glycosaminoglycans (GAG). GAGs, strategically located in the pericellular and extracellular space, bind developmentally active growth factors and morphogenes such as fibroblast growth factors (FGF), transforming growth factor- (TGF-) and bone morphogenetic proteins (BMPs) aside from cytokines. These interactions affect activities in many cells, including stem cells, important in development and tissue regeneration. Moreover, it is becoming clear that the "inherent code", such as sulfation of disaccharides of GAGs is a strong determinant of cellular outcome. Sulfation pattern, deacetylations and epimerizations of GAG chains function as tuning forks in gradient formation of morphogens, growth factors and cytokines. Learning to tune these fine instruments, i.e. interactions between growth factors (GF), chemokines and cytokines with the specific disaccharide code of GAGs in the adult lung, could become the key to unlock inherent regenerative forces to override pathological remodeling. This review aims to give an overview of the role GAGs play during development and similar events in regenerative efforts in the adult lung.

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  • Cell and Molecular Biology
Original languageEnglish
Pages (from-to)823-832
Number of pages10
JournalStem Cells and Development
Volume28
Issue number13
Publication statusPublished - 2019 Jun 27
Publication categoryResearch
Peer-reviewedYes