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Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis.

Ghatak S, Maytin EV, Mack JA, Hascall VC, Atanelishvili I, Moreno Rodriguez R, Markwald RR, Misra S - Int J Cell Biol (2015)

Bottom Line: Fibrosis is a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis).Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes.Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

ABSTRACT
A wound is a type of injury that damages living tissues. In this review, we will be referring mainly to healing responses in the organs including skin and the lungs. Fibrosis is a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis). In tissues such as the skin, the repair of the dermis after wounding requires not only the fibroblasts that produce the ECM molecules, but also the overlying epithelial layer (keratinocytes), the endothelial cells, and smooth muscle cells of the blood vessel and white blood cells such as neutrophils and macrophages, which together orchestrate the cytokine-mediated signaling and paracrine interactions that are required to regulate the proper extent and timing of the repair process. This review will focus on the importance of extracellular molecules in the microenvironment, primarily the proteoglycans and glycosaminoglycan hyaluronan, and their roles in wound healing. First, we will briefly summarize the physiological, cellular, and biochemical elements of wound healing, including the importance of cytokine cross-talk between cell types. Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes. Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.

No MeSH data available.


Related in: MedlinePlus

Diagram of part of an aggrecan aggregate. G1, G2, and G3 are globular, folded regions of the central core protein. Proteoglycan aggrecan showing the noncovalent binding of proteoglycan to HA with the link proteins.
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fig2: Diagram of part of an aggrecan aggregate. G1, G2, and G3 are globular, folded regions of the central core protein. Proteoglycan aggrecan showing the noncovalent binding of proteoglycan to HA with the link proteins.

Mentions: PGs have core proteins or glycoproteins with large GAG side-chains (Figure 2), and they participate in cell-cell and cell-matrix interactions, cell proliferation, and migration, and in cytokine and growth factor signaling associated with wound healing. Small leucine-rich PGs (SLRPs) and the chondroitin sulfate PG versican are found in the dermis of wounds, the PG perlecan in the basement membrane, and the heparan sulfate PGs, syndecans, and glypicans on the cell surfaces. The versican-v3 isoform promotes transition of normal dermal fibroblasts to myofibroblasts [46, 47]. Perlecan regulates wound healing through induction of angiogenesis [48]. Increased expression of syndecans-1 and syndecans-4 in wounds [49] stimulates keratinocyte [50] and endothelial cell migration and angiogenesis in mice [51]. Decorin, a member of the SLRP family, negatively regulates TGF-β1 [52] and demonstrates effects of antifibrosis in various tissues, including kidney [53], muscle [54], and lung [55]. GAG chains covalently bound to the core protein of PGs dominate their physical properties. PGs can maintain the ECM in a hydrated condition, exclude other macromolecules, and allow permeability of low molecular weight solutes. Thus, by interacting with other ECM components, PGs are critical to organize the matrix [56, 57].


Roles of Proteoglycans and Glycosaminoglycans in Wound Healing and Fibrosis.

Ghatak S, Maytin EV, Mack JA, Hascall VC, Atanelishvili I, Moreno Rodriguez R, Markwald RR, Misra S - Int J Cell Biol (2015)

Diagram of part of an aggrecan aggregate. G1, G2, and G3 are globular, folded regions of the central core protein. Proteoglycan aggrecan showing the noncovalent binding of proteoglycan to HA with the link proteins.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4581578&req=5

fig2: Diagram of part of an aggrecan aggregate. G1, G2, and G3 are globular, folded regions of the central core protein. Proteoglycan aggrecan showing the noncovalent binding of proteoglycan to HA with the link proteins.
Mentions: PGs have core proteins or glycoproteins with large GAG side-chains (Figure 2), and they participate in cell-cell and cell-matrix interactions, cell proliferation, and migration, and in cytokine and growth factor signaling associated with wound healing. Small leucine-rich PGs (SLRPs) and the chondroitin sulfate PG versican are found in the dermis of wounds, the PG perlecan in the basement membrane, and the heparan sulfate PGs, syndecans, and glypicans on the cell surfaces. The versican-v3 isoform promotes transition of normal dermal fibroblasts to myofibroblasts [46, 47]. Perlecan regulates wound healing through induction of angiogenesis [48]. Increased expression of syndecans-1 and syndecans-4 in wounds [49] stimulates keratinocyte [50] and endothelial cell migration and angiogenesis in mice [51]. Decorin, a member of the SLRP family, negatively regulates TGF-β1 [52] and demonstrates effects of antifibrosis in various tissues, including kidney [53], muscle [54], and lung [55]. GAG chains covalently bound to the core protein of PGs dominate their physical properties. PGs can maintain the ECM in a hydrated condition, exclude other macromolecules, and allow permeability of low molecular weight solutes. Thus, by interacting with other ECM components, PGs are critical to organize the matrix [56, 57].

Bottom Line: Fibrosis is a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis).Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes.Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.

View Article: PubMed Central - PubMed

Affiliation: Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA.

ABSTRACT
A wound is a type of injury that damages living tissues. In this review, we will be referring mainly to healing responses in the organs including skin and the lungs. Fibrosis is a process of dysregulated extracellular matrix (ECM) production that leads to a dense and functionally abnormal connective tissue compartment (dermis). In tissues such as the skin, the repair of the dermis after wounding requires not only the fibroblasts that produce the ECM molecules, but also the overlying epithelial layer (keratinocytes), the endothelial cells, and smooth muscle cells of the blood vessel and white blood cells such as neutrophils and macrophages, which together orchestrate the cytokine-mediated signaling and paracrine interactions that are required to regulate the proper extent and timing of the repair process. This review will focus on the importance of extracellular molecules in the microenvironment, primarily the proteoglycans and glycosaminoglycan hyaluronan, and their roles in wound healing. First, we will briefly summarize the physiological, cellular, and biochemical elements of wound healing, including the importance of cytokine cross-talk between cell types. Second, we will discuss the role of proteoglycans and hyaluronan in regulating these processes. Finally, approaches that utilize these concepts as potential therapies for fibrosis are discussed.

No MeSH data available.


Related in: MedlinePlus