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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

Schematic presentation of changes in hyaluronan synthesis/molecular size and cellular events and matrix events during the course of wound healing and fibrosis. Many of the biological processes mediated by HA are crucial for wound healing and fibrosis. After injury, wound healing follows a tightly regulated sequence of events. These phases are inflammation, granulation tissue formation, proliferation, reepithelization, and remodelling. In the early phases, high molecular HA is degraded by reactive oxygen species from activated granulocytes and by hyaluronidases secreted from platelets. Then monocytes secrete inflammatory mediators, which attract additional inflammatory cells. Keratinocytes become activated to migrate, proliferate, and to synthesize HA. As a result the LMW degradation products are active inducers of angiogenesis and inflammation. At later stages the interim matrix becomes supplemented with newly synthesized HMW HA, which contributes to tissue remodelling. During repetitive injury, the repairing processes are hindered, and the keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel, neutrophils, and macrophages together orchestrate the increased cytokine-mediated signaling and augment HA-CD44 signaling and excess collagen production that results in fibrosis.
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Related In: Results  -  Collection


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fig1: Schematic presentation of changes in hyaluronan synthesis/molecular size and cellular events and matrix events during the course of wound healing and fibrosis. Many of the biological processes mediated by HA are crucial for wound healing and fibrosis. After injury, wound healing follows a tightly regulated sequence of events. These phases are inflammation, granulation tissue formation, proliferation, reepithelization, and remodelling. In the early phases, high molecular HA is degraded by reactive oxygen species from activated granulocytes and by hyaluronidases secreted from platelets. Then monocytes secrete inflammatory mediators, which attract additional inflammatory cells. Keratinocytes become activated to migrate, proliferate, and to synthesize HA. As a result the LMW degradation products are active inducers of angiogenesis and inflammation. At later stages the interim matrix becomes supplemented with newly synthesized HMW HA, which contributes to tissue remodelling. During repetitive injury, the repairing processes are hindered, and the keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel, neutrophils, and macrophages together orchestrate the increased cytokine-mediated signaling and augment HA-CD44 signaling and excess collagen production that results in fibrosis.

Mentions: Wound healing involves integrated and overlapping phases: (a) haemostasis, (b) inflammation, (c) proliferation, and (d) remodelling (Figure 1).


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)

Schematic presentation of changes in hyaluronan synthesis/molecular size and cellular events and matrix events during the course of wound healing and fibrosis. Many of the biological processes mediated by HA are crucial for wound healing and fibrosis. After injury, wound healing follows a tightly regulated sequence of events. These phases are inflammation, granulation tissue formation, proliferation, reepithelization, and remodelling. In the early phases, high molecular HA is degraded by reactive oxygen species from activated granulocytes and by hyaluronidases secreted from platelets. Then monocytes secrete inflammatory mediators, which attract additional inflammatory cells. Keratinocytes become activated to migrate, proliferate, and to synthesize HA. As a result the LMW degradation products are active inducers of angiogenesis and inflammation. At later stages the interim matrix becomes supplemented with newly synthesized HMW HA, which contributes to tissue remodelling. During repetitive injury, the repairing processes are hindered, and the keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel, neutrophils, and macrophages together orchestrate the increased cytokine-mediated signaling and augment HA-CD44 signaling and excess collagen production that results in fibrosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig1: Schematic presentation of changes in hyaluronan synthesis/molecular size and cellular events and matrix events during the course of wound healing and fibrosis. Many of the biological processes mediated by HA are crucial for wound healing and fibrosis. After injury, wound healing follows a tightly regulated sequence of events. These phases are inflammation, granulation tissue formation, proliferation, reepithelization, and remodelling. In the early phases, high molecular HA is degraded by reactive oxygen species from activated granulocytes and by hyaluronidases secreted from platelets. Then monocytes secrete inflammatory mediators, which attract additional inflammatory cells. Keratinocytes become activated to migrate, proliferate, and to synthesize HA. As a result the LMW degradation products are active inducers of angiogenesis and inflammation. At later stages the interim matrix becomes supplemented with newly synthesized HMW HA, which contributes to tissue remodelling. During repetitive injury, the repairing processes are hindered, and the keratinocytes, the endothelial cells, and smooth muscle cells of the blood vessel, neutrophils, and macrophages together orchestrate the increased cytokine-mediated signaling and augment HA-CD44 signaling and excess collagen production that results in fibrosis.
Mentions: Wound healing involves integrated and overlapping phases: (a) haemostasis, (b) inflammation, (c) proliferation, and (d) remodelling (Figure 1).

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