Hyaluronan in Tissue Injury and Repair
Abstract
A hallmark of tissue injury and repair is the turnover of extracellular matrix components. This review focuses on the role of the glycosaminoglycan hyaluronan in tissue injury and repair. Both the synthesis and degradation of extracellular matrix are critical contributors to tissue repair and remodeling. Fragmented hyaluronan accumulates during tissue injury and functions in ways distinct from the native polymer. There is accumulating evidence that hyaluronan degradation products can stimulate the expression of inflammatory genes by a variety of immune cells at the injury site. CD44 is the major cell-surface hyaluronan receptor and is required to clear hyaluronan degradation products produced during lung injury; impaired clearance of hyaluronan results in persistent inflammation. However, hyaluronan fragment stimulation of inflammatory gene expression is not dependent on CD44 in inflammatory macrophages. Instead, hyaluronan fragments utilize both Toll-like receptor (TLR) 4 and TLR2 to stimulate inflammatory genes in macrophages. Hyaluronan also is present on the cell surface of lung alveolar epithelial cells and provides protection against tissue damage by interacting with TLR2 and TLR4 on these parenchymal cells. The simple repeating structure of hyaluronan appears to be involved in a number of important aspects of noninfectious tissue injury and repair that are dependent on the size and location of the polymer as well as the interacting cells. Thus, the interactions between the endogenous matrix component hyaluronan and its signaling receptors initiate inflammatory responses, maintain structural cell integrity, and promote recovery from tissue injury.
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In the body, HA interacts with proteins such as CD44 and RHAMM, which play roles in cell signaling, migration, and inflammation.
“In the body, HA interacts with proteins, such as CD44 and Receptor for Hyaluronan Mediated Motility (RHAMM), which play roles in cell signaling, migration, and inflammation (Figure 6) [122,123].”
From Biomaterials in Postoperative Adhesion Barriers and Uterine Tissue Engineering (2025) · cites this paper as [122]
Hyaluronan is directly recognized by TLR2 and TLR4.
“Hyaluronan is also directly recognized by TLR2 and TLR4, and this interaction was shown to have a role in mediating inflammatory responses in a mouse model of sterile bleomycin-induced lung injury102.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [102]
The interaction of hyaluronan with TLR2 and TLR4 has a role in mediating inflammatory responses in a mouse model of sterile bleomycin-induced lung injury.
“Hyaluronan is also directly recognized by TLR2 and TLR4, and this interaction was shown to have a role in mediating inflammatory responses in a mouse model of sterile bleomycin-induced lung injury102.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [102]
Hyaluronan fragments can signal through CD44, leading to MAPK activation.
“Hyaluronan fragments, for example, can signal through CD44, leading to MAPK activation102.”
From Sterile inflammation: sensing and reacting to damage (2010) · cites this paper as [102]
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- Authors
- Jiang, D., Liang, J., & Noble, P. W.
- Affiliations
- Duke University (US)
- Venue
- Annual Review of Cell and Developmental Biology
- Publisher
- Annual Reviews
- Published
- 2007-11-01
- Volume
- 23
- Issue
- 1
- Pages
- 435-461
- ISSN
- 1081-0706 (ISSN-L)
- 1530-8995
- OpenAlex
- W2117566184
- Cited by
- 835
- References
- 157
- Citations by year
- 2026: 27 · 2025: 29 · 2024: 27 · 2023: 30 · 2022: 39 · 2021: 33 · 2020: 46 · 2019: 42 · 2018: 49 · 2017: 35 · 2016: 54 · 2015: 45 · 2014: 65 · 2013: 39 · 2012: 60
- FWCI
- 3.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Cell and Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Proteoglycans and glycosaminoglycans research
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
- Keywords
- hyaluronic acid, tissue damage, tissue repair, extracellular matrix turnover, CD44, lung injury, inflammation, macrophages, TLR4, TLR2, alveolar epithelial cells, glycosaminoglycans, extracellular matrix remodeling
- MeSH terms
- Hyaluronan Synthases, Animals, Humans, Hyaluronic Acid, Immunity, Regeneration, Glucuronosyltransferase, Wound Healing, Signal Transduction, Hyaluronan Receptors, Toll-Like Receptors
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