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The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response.

Record Type:	Electronic resources : Monograph/item
Title/Author:	The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response./
Author:	Marshall, Payton Lachlan.
Description:	1 online resource (293 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 84-04, Section: A.
Contained By:	Dissertations Abstracts International84-04A.
Subject:	T cell receptors. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=29342272click for full text (PQDT)
ISBN:	9798351495828

The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response.
Marshall, Payton Lachlan.

The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response. - 1 online resource (293 pages)

Source: Dissertations Abstracts International, Volume: 84-04, Section: A.

Thesis (Ph.D.)--Stanford University, 2022.

Includes bibliographical references

Hyaluronan (HA) is a disaccharide polymer consisting of glucuronic acid and N-acetyl glucosamine that dominates the extracellular space in the eukaryotic body. HA serves many roles; it is a vital structural component of tissue and plays important regulatory roles in the homeostasis of all organs. As part of the pericellular matrix (PCM), HA is extruded outward from the cell membrane in the mesh of proteins and sugars that make up the glycocalyx. This thick coat, consisting predominantly of HA, dominates the interface between a cell and its environment. HA plays an important role in cell communication within the extracellular space, and the regulation of HA and it's signaling is of vital importance. HA is produced by cell surface synthases (HAS1, HAS2, HAS3) that polymerize and extrude the polymer into the extracellular space. Hyaluronidases (HYAL) digest high molecular weight strands down to short low molecular weight HA. Extracellularly, HA is organized by hyaladherins that cross-link and stabilize the matrix, creating higher orders of PCM organization.The composition and integrity of HA that surrounds cells provides an important environmental cue that drives the growth and activity of a cell. There are multiple extracellular receptors that bind HA. The main HA receptor is CD44, which binds extracellular HA and transmits this signal through cross-linking, thereby controlling basic cellular functions such as growth as well as more specialized activities depending on cell lineage. HA plays an important role in tissue structure. Due to its highly hydroscopic nature, HA can sequester water and charged molecules across tissues to alter their physical properties. Through its adhesive properties, HA can also assist in the cell's ability to migrate throughout tissue and stabilize its position. Dysregulation of HA production and maintenance promotes pathophysiology of both acute and chronic diseases. Specifically, HA's role in inflammatory regulation means that loss of homeostatic control of HA production quickly leads to a variety of disease states, most notably autoimmunity and chronic tissue destruction. HA targeting therapies remain limited in availability, despite likely efficacy in treating autoimmune diseases and chronic inflammatory pathologies. Small molecule interventions are limited to essentially one repurposed antispasmodic developed in the mid-20th century: 4-methylumbelliferone (4-MU). Despite its potent effects on HA-mediated diseases and excellent safety profile, further small molecule interventions have not been pursued until recently. Biologics also represent a possible realm of HA intervention that has only just begun to be explored. Synthetically derived hyaluronidases and HA itself may provide potent local effects antagonizing or promoting immune system activities.In this thesis I will discuss the biological role of HA in chronic and acute disease. I focus on how dysregulation of HA production potentiates pathophysiology of three different inflammatory states: chronic asthma, type II diabetes, and solid organ transplantation. Moreover, I present investigations into 4-MU treatment to protect against inflammatory pathologies. Lastly, I present investigations looking at developing new interventions that can add to our repertoire of HA targeting therapies. In Chapter 2 I discuss the HA composition of the asthmatic lung.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2023

Mode of access: World Wide Web

ISBN: 9798351495828Subjects--Topical Terms:

3561758
T cell receptors.
Index Terms--Genre/Form:

542853
Electronic books.

The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response.
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245 1 4 $a The Role of Hyaluronic Acid in Regulating Inflammation and the Immune Response.
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300 $a 1 online resource (293 pages)
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500 $a Source: Dissertations Abstracts International, Volume: 84-04, Section: A.
500 $a Advisor: Engleman, Edgar G; Heilshorn, Sarah; Maltzman, Jonathan; Meyer, Everett.
502 $a Thesis (Ph.D.)--Stanford University, 2022.
504 $a Includes bibliographical references
520 $a Hyaluronan (HA) is a disaccharide polymer consisting of glucuronic acid and N-acetyl glucosamine that dominates the extracellular space in the eukaryotic body. HA serves many roles; it is a vital structural component of tissue and plays important regulatory roles in the homeostasis of all organs. As part of the pericellular matrix (PCM), HA is extruded outward from the cell membrane in the mesh of proteins and sugars that make up the glycocalyx. This thick coat, consisting predominantly of HA, dominates the interface between a cell and its environment. HA plays an important role in cell communication within the extracellular space, and the regulation of HA and it's signaling is of vital importance. HA is produced by cell surface synthases (HAS1, HAS2, HAS3) that polymerize and extrude the polymer into the extracellular space. Hyaluronidases (HYAL) digest high molecular weight strands down to short low molecular weight HA. Extracellularly, HA is organized by hyaladherins that cross-link and stabilize the matrix, creating higher orders of PCM organization.The composition and integrity of HA that surrounds cells provides an important environmental cue that drives the growth and activity of a cell. There are multiple extracellular receptors that bind HA. The main HA receptor is CD44, which binds extracellular HA and transmits this signal through cross-linking, thereby controlling basic cellular functions such as growth as well as more specialized activities depending on cell lineage. HA plays an important role in tissue structure. Due to its highly hydroscopic nature, HA can sequester water and charged molecules across tissues to alter their physical properties. Through its adhesive properties, HA can also assist in the cell's ability to migrate throughout tissue and stabilize its position. Dysregulation of HA production and maintenance promotes pathophysiology of both acute and chronic diseases. Specifically, HA's role in inflammatory regulation means that loss of homeostatic control of HA production quickly leads to a variety of disease states, most notably autoimmunity and chronic tissue destruction. HA targeting therapies remain limited in availability, despite likely efficacy in treating autoimmune diseases and chronic inflammatory pathologies. Small molecule interventions are limited to essentially one repurposed antispasmodic developed in the mid-20th century: 4-methylumbelliferone (4-MU). Despite its potent effects on HA-mediated diseases and excellent safety profile, further small molecule interventions have not been pursued until recently. Biologics also represent a possible realm of HA intervention that has only just begun to be explored. Synthetically derived hyaluronidases and HA itself may provide potent local effects antagonizing or promoting immune system activities.In this thesis I will discuss the biological role of HA in chronic and acute disease. I focus on how dysregulation of HA production potentiates pathophysiology of three different inflammatory states: chronic asthma, type II diabetes, and solid organ transplantation. Moreover, I present investigations into 4-MU treatment to protect against inflammatory pathologies. Lastly, I present investigations looking at developing new interventions that can add to our repertoire of HA targeting therapies. In Chapter 2 I discuss the HA composition of the asthmatic lung.
533 $a Electronic reproduction. $b Ann Arbor, Mich. : $c ProQuest, $d 2023
538 $a Mode of access: World Wide Web
650 4 $a T cell receptors. $3 3561758
650 4 $a Signal transduction. $3 3546420
650 4 $a Hyperglycemia. $3 3700431
650 4 $a Transplants & implants. $3 3562683
650 4 $a Antigen presentation. $3 3564522
650 4 $a Blood vessels. $3 3561732
650 4 $a Immune system. $3 689864
650 4 $a Polymerization. $3 560492
650 4 $a Binding sites. $3 3560349
650 4 $a Cytokines. $3 687114
650 4 $a Lymphocytes. $3 895384
650 4 $a Cartilage. $3 924011
650 4 $a Allergies. $3 3680820
650 4 $a Families & family life. $3 3422406
650 4 $a Inflammatory diseases. $3 3561779
650 4 $a Adhesives. $3 871837
650 4 $a Phosphorylation. $3 816803
650 4 $a Heparan sulfate. $3 3560745
650 4 $a Apoptosis. $3 600650
650 4 $a Cell growth. $3 3560747
650 4 $a Cellular biology. $3 3172791
650 4 $a Immunology. $3 611031
650 4 $a Individual & family studies. $3 2122770
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710 2 $a Stanford University. $3 754827
773 0 $t Dissertations Abstracts International $g 84-04A.
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