ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing

A buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiol...

Full description

Bibliographic Details
Main Authors: Xiao Lin, Isabel Y. Moreno, Lawrence Nguyen, Tarsis F. Gesteira, Vivien J. Coulson-Thomas
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/13/9/1385
_version_ 1797581096305557504
author Xiao Lin
Isabel Y. Moreno
Lawrence Nguyen
Tarsis F. Gesteira
Vivien J. Coulson-Thomas
author_facet Xiao Lin
Isabel Y. Moreno
Lawrence Nguyen
Tarsis F. Gesteira
Vivien J. Coulson-Thomas
author_sort Xiao Lin
collection DOAJ
description A buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiological properties remain largely unknown. This study characterized the molecular weight (MW), structures, and physiological properties of oxHA. For this, high-molecular-weight HA (HMWHA) was oxidized using increasing molar ratios of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) or hypochlorous acid (HOCl). ROS lead to the fragmentation of HA, with the oxHA products produced by HOCl exhibiting an altered chemical structure while those produced by H<sub>2</sub>O<sub>2</sub> do not. HMWHA promotes the viability of human corneal epithelial cells (hTCEpi), while low MWHA (LMWHA), ultra-LMWHA (ULMWHA), and most forms of oxHA do not. HMWHA and LMWHA promote hTCEpi proliferation, while ULMWHA and all forms of oxHA do not. LMWHA and some forms of oxHA promote hTCEpi migration, while HMWHA does not. Finally, all native forms of HA and oxHA produced by HOCl promote in vivo corneal wound healing, while oxHA produced by H<sub>2</sub>O<sub>2</sub> does not. Taken together, our results show that HA fragmentation by ROS can alter the physiological activity of HA by altering its MW and structure.
first_indexed 2024-03-10T22:59:21Z
format Article
id doaj.art-6adcde4d5fb345f5b4f2414e08b9ab7b
institution Directory Open Access Journal
issn 2218-273X
language English
last_indexed 2024-03-10T22:59:21Z
publishDate 2023-09-01
publisher MDPI AG
record_format Article
series Biomolecules
spelling doaj.art-6adcde4d5fb345f5b4f2414e08b9ab7b2023-11-19T09:46:15ZengMDPI AGBiomolecules2218-273X2023-09-01139138510.3390/biom13091385ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound HealingXiao Lin0Isabel Y. Moreno1Lawrence Nguyen2Tarsis F. Gesteira3Vivien J. Coulson-Thomas4College of Optometry, University of Houston, 4401 Martin Luther King Boulevard, Houston, TX 77204-2020, USACollege of Optometry, University of Houston, 4401 Martin Luther King Boulevard, Houston, TX 77204-2020, USACollege of Optometry, University of Houston, 4401 Martin Luther King Boulevard, Houston, TX 77204-2020, USACollege of Optometry, University of Houston, 4401 Martin Luther King Boulevard, Houston, TX 77204-2020, USACollege of Optometry, University of Houston, 4401 Martin Luther King Boulevard, Houston, TX 77204-2020, USAA buildup of reactive oxygen species (ROS) occurs in virtually all pathological conditions. Hyaluronan (HA) is a major extracellular matrix component and is susceptible to oxidation by reactive oxygen species (ROS), yet the precise chemical structures of oxidized HA products (oxHA) and their physiological properties remain largely unknown. This study characterized the molecular weight (MW), structures, and physiological properties of oxHA. For this, high-molecular-weight HA (HMWHA) was oxidized using increasing molar ratios of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) or hypochlorous acid (HOCl). ROS lead to the fragmentation of HA, with the oxHA products produced by HOCl exhibiting an altered chemical structure while those produced by H<sub>2</sub>O<sub>2</sub> do not. HMWHA promotes the viability of human corneal epithelial cells (hTCEpi), while low MWHA (LMWHA), ultra-LMWHA (ULMWHA), and most forms of oxHA do not. HMWHA and LMWHA promote hTCEpi proliferation, while ULMWHA and all forms of oxHA do not. LMWHA and some forms of oxHA promote hTCEpi migration, while HMWHA does not. Finally, all native forms of HA and oxHA produced by HOCl promote in vivo corneal wound healing, while oxHA produced by H<sub>2</sub>O<sub>2</sub> does not. Taken together, our results show that HA fragmentation by ROS can alter the physiological activity of HA by altering its MW and structure.https://www.mdpi.com/2218-273X/13/9/1385high-molecular-weight hyaluronanlow-molecular-weight hyaluronanoxidative stresswound healingcorneal epithelium
spellingShingle Xiao Lin
Isabel Y. Moreno
Lawrence Nguyen
Tarsis F. Gesteira
Vivien J. Coulson-Thomas
ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
Biomolecules
high-molecular-weight hyaluronan
low-molecular-weight hyaluronan
oxidative stress
wound healing
corneal epithelium
title ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
title_full ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
title_fullStr ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
title_full_unstemmed ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
title_short ROS-Mediated Fragmentation Alters the Effects of Hyaluronan on Corneal Epithelial Wound Healing
title_sort ros mediated fragmentation alters the effects of hyaluronan on corneal epithelial wound healing
topic high-molecular-weight hyaluronan
low-molecular-weight hyaluronan
oxidative stress
wound healing
corneal epithelium
url https://www.mdpi.com/2218-273X/13/9/1385
work_keys_str_mv AT xiaolin rosmediatedfragmentationalterstheeffectsofhyaluronanoncornealepithelialwoundhealing
AT isabelymoreno rosmediatedfragmentationalterstheeffectsofhyaluronanoncornealepithelialwoundhealing
AT lawrencenguyen rosmediatedfragmentationalterstheeffectsofhyaluronanoncornealepithelialwoundhealing
AT tarsisfgesteira rosmediatedfragmentationalterstheeffectsofhyaluronanoncornealepithelialwoundhealing
AT vivienjcoulsonthomas rosmediatedfragmentationalterstheeffectsofhyaluronanoncornealepithelialwoundhealing