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International Journal of Molecular... Mar 2021With the burgeoning interest in hyaluronic acid (HA) in recent years, hyaluronidases (HYALs) have come to light for their role in regulating catabolism of HA and its... (Review)
Review
With the burgeoning interest in hyaluronic acid (HA) in recent years, hyaluronidases (HYALs) have come to light for their role in regulating catabolism of HA and its molecular weight (MW) distribution in various tissues. Of the six hyaluronidase-like gene sequences in the human genome, and are of particular significance because they are the primary hyaluronidases active in human somatic tissue. Perhaps more importantly, for the sake of this review, they cleave anti-inflammatory and anti-fibrotic high-molecular-weight HA into pro-inflammatory and pro-fibrotic oligosaccharides. With this, HYALs regulate HA degradation and thus the development and progression of various diseases. Given the dearth of literature focusing specifically on HYALs in the past decade, this review seeks to expound their role in human diseases of the skin, heart, kidneys, and more. The review will delve into the molecular mechanisms and pathways of HYALs and discuss current and potential future therapeutic benefits of HYALs as a clinical treatment.
Topics: Animals; Disease Management; Disease Susceptibility; Drug Development; Gene Expression Regulation; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Multigene Family; Organ Specificity
PubMed: 33809827
DOI: 10.3390/ijms22063204 -
Pain Physician Nov 2019Neuroplasty, also known as percutaneous adhesiolysis, is an effective treatment for persistent axial and radicular pain. (Review)
Review
BACKGROUND
Neuroplasty, also known as percutaneous adhesiolysis, is an effective treatment for persistent axial and radicular pain.
OBJECTIVES
One issue of concern is whether hyaluronidase should be used when performing neuroplasty. The objective of this narrative review is to evaluate the current literature relating to hyaluronidase and its role in neuroplasty.
METHODS
The literature relating to hyaluronidase was examined via a search of PubMed and Google Scholar until April 2019, review of the citations of relevant literature, and the authors' knowledge of the literature and activity in the field. The literature was reviewed in light of hyaluronidase's physiologic role, allergenicity, medical uses, and evaluation specifically for neuroplasty.
RESULTS
Hyaluronidase facilitates the spread of medications in the extracellular matrix by breaking down polysaccharides in the interstitial space. While allergic reactions to hyaluronidase have been reported, these reactions occurred with animal-derived preparations. The current human recombinant hyaluronidase does not have any reports of allergic reactions. Laboratory studies show that it does not evoke an immune response. Hyaluronidase has been extensively used in a variety of medical applications, including intrathecal treatment of arachnoiditis.There have been multiple studies reporting benefit from the use of hyaluronidase in interventional procedures. One randomized trial specifically looking at the use of hyaluronidase in neuroplasty found that the addition of hyaluronidase improved pain ratings at 12 months compared to other techniques and decreased the number of procedures needed to gain effect.
LIMITATIONS
There have been limited studies examining the enhanced efficacy of neuroplasty when hyaluronidase is added.
CONCLUSIONS
Because of enhanced efficacy and safety, and because of the decrease in the number of procedures needed to be performed, hyaluronidase should be considered when deciding which medications to use when performing neuroplasty.
KEY WORDS
Neuroplasty, adhesiolysis, hyaluronidase, spinal stenosis, failed back surgery synderome, post lumbar surgery syndrome.
Topics: Humans; Hyaluronoglucosaminidase; Lumbosacral Region; Neurosurgical Procedures; Pain; Pain Management; Spinal Stenosis; Treatment Outcome
PubMed: 31775402
DOI: No ID Found -
British Journal of Anaesthesia Sep 1993
Review
Topics: Anesthesia, Local; Anesthetics, Local; Animals; Humans; Hyaluronoglucosaminidase; Nerve Block; Ophthalmology
PubMed: 8398527
DOI: 10.1093/bja/71.3.422 -
Frontiers in Immunology 2019Hyaluronan (HA) is a glycosaminoglycan with a simple structure but diverse and often opposing functions. The biological activities of this polysaccharide depend on its... (Review)
Review
Hyaluronan (HA) is a glycosaminoglycan with a simple structure but diverse and often opposing functions. The biological activities of this polysaccharide depend on its molecular weight and the identity of interacting receptors. HA is initially synthesized as high molecular-weight (HMW) polymers, which maintain homeostasis and restrain cell proliferation and migration in normal tissues. These HMW-HA functions are mediated by constitutively expressed receptors including CD44, LYVE-1, and STABILIN2. During normal processes such as tissue remodeling and wound healing, HMW-HA is fragmented into low molecular weight polymers (LMW-HA) by hyaluronidases and free radicals, which promote inflammation, immune cell recruitment and the epithelial cell migration. These functions are mediated by RHAMM and TLR2,4, which coordinate signaling with CD44 and other HA receptors. Tumor cells hijack the normally tightly regulated HA production/fragmentation associated with wound repair/remodeling, and these HA functions participate in driving and maintaining malignant progression. However, elevated HMW-HA production in the absence of fragmentation is linked to cancer resistance. The controlled production of HA polymer sizes and their functions are predicted to be key to dissecting the role of microenvironment in permitting or restraining the oncogenic potential of tissues. This review focuses on the dual nature of HA in cancer initiation vs. resistance, and the therapeutic potential of HA for chemo-prevention and as a target for cancer management.
Topics: Animals; Humans; Hyaluronan Receptors; Hyaluronic Acid; Hyaluronoglucosaminidase; Neoplasms; Tumor Microenvironment
PubMed: 31134064
DOI: 10.3389/fimmu.2019.00947 -
Gastroenterology Nov 2022The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and...
BACKGROUND & AIMS
The stroma in pancreatic ductal adenocarcinoma (PDAC) contributes to its immunosuppressive nature and therapeutic resistance. Herein we sought to modify signaling and enhance immunotherapy efficacy by targeting multiple stromal components through both intracellular and extracellular mechanisms.
METHODS
A murine liver metastasis syngeneic model of PDAC was treated with focal adhesion kinase inhibitor (FAKi), anti-programmed cell death protein 1 (PD-1) antibody, and stromal hyaluronan (HA) degradation by PEGylated recombinant human hyaluronidase (PEGPH20) to assess immune and stromal modulating effects of these agents and their combinations.
RESULTS
The results showed that HA degradation by PEGPH20 and reduction in phosphorylated FAK expression by FAKi leads to improved survival in PDAC-bearing mice treated with anti-PD-1 antibody. HA degradation in combination with FAKi and anti-PD-1 antibody increases T-cell infiltration and alters T-cell phenotype toward effector memory T cells. FAKi alters the expression of T-cell modulating cytokines and leads to changes in T-cell metabolism and increases in effector T-cell signatures. HA degradation in combination with anti-PD-1 antibody and FAKi treatments reduces granulocytes, including granulocytic- myeloid-derived suppressor cells and decreases C-X-C chemokine receptor type 4 (CXCR4)-expressing myeloid cells, particularly the CXCR4-expressing granulocytes. Anti-CXCR4 antibody combined with FAKi and anti-PD-1 antibody significantly decreases metastatic rates in the PDAC liver metastasis model.
CONCLUSIONS
This represents the first preclinical study to identify synergistic effects of targeting both intracellular and extracellular components within the PDAC stroma and supports testing anti-CXCR4 antibody in combination with FAKi as a PDAC treatment strategy.
Topics: Humans; Mice; Animals; Pancreatic Neoplasms; Adenocarcinoma; Hyaluronoglucosaminidase; Hyaluronic Acid; Carcinoma, Pancreatic Ductal; Liver Neoplasms; Focal Adhesion Protein-Tyrosine Kinases; Cytokines; Cell Death; Polyethylene Glycols; Tumor Microenvironment
PubMed: 35718227
DOI: 10.1053/j.gastro.2022.06.027 -
Biomedicine & Pharmacotherapy =... Sep 2023HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes... (Review)
Review
HYBID is a new hyaluronan-degrading enzyme and exists in various cells of the human body. Recently, HYBID was found to over-express in the osteoarthritic chondrocytes and fibroblast-like synoviocytes. According to these researches, high level of HYBID is significantly correlated with cartilage degeneration in joints and hyaluronic acid degradation in synovial fluid. In addition, HYBID can affect inflammatory cytokine secretion, cartilage and synovium fibrosis, synovial hyperplasia via multiple signaling pathways, thereby exacerbating osteoarthritis. Based on the existing research of HYBID in osteoarthritis, HYBID can break the metabolic balance of HA in joints through the degradation ability independent of HYALs/CD44 system and furthermore affect cartilage structure and mechanotransduction of chondrocytes. In particular, in addition to HYBID itself being able to trigger some signaling pathways, we believe that low-molecular-weight hyaluronan produced by excess degradation can also stimulate some disease-promoting signaling pathways by replacing high-molecular-weight hyaluronan in joints. The specific role of HYBID in osteoarthritis is gradually revealed, and the discovery of HYBID raises the new way to treat osteoarthritis. In this review, the expression and basic functions of HYBID in joints were summarized, and reveal potential role of HYBID as a key target in treatment for osteoarthritis.
Topics: Humans; Hyaluronic Acid; Mechanotransduction, Cellular; Osteoarthritis; Hyaluronoglucosaminidase; Disease Progression
PubMed: 37364478
DOI: 10.1016/j.biopha.2023.115043 -
Anaesthesia Sep 2015
Topics: Amides; Anesthetics, Local; Brachial Plexus; Brachial Plexus Block; Female; Humans; Hyaluronoglucosaminidase; Male
PubMed: 26263866
DOI: 10.1111/anae.13195 -
Biomolecules Feb 2022Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in a variety of biological processes. Half of the total amount of HA in...
Hyaluronan (HA) comprises a fundamental component of the extracellular matrix and participates in a variety of biological processes. Half of the total amount of HA in the human body is present in the skin. HA exhibits a dynamic turnover; its half-life in the skin is less than one day. Nevertheless, the specific participants in the catabolism of HA in the skin have not yet been described in detail, despite the essential role of HA in cutaneous biology. A deeper knowledge of the processes involved will act to support the development of HA-based topical and implantable materials and enhance the understanding of the various related pathological cutaneous conditions. This study aimed to characterize the distribution and activity of hyaluronidases and the other proteins involved in the degradation of HA in healthy human full-thickness skin, the epidermis and the dermis. Hyaluronidase activity was detected for the first time in healthy human skin. The degradation of HA occurred in lysates at an acidic pH. HA gel zymography revealed a single band corresponding to approximately 50 kDa. This study provided the first comprehensive view of the distribution of canonic HA-degrading proteins (HYAL1 and HYAL2) in human skin employing IHF and IHC. Furthermore, contrary to previous assumptions TMEM2, a novel hyaluronidase, as well as CEMIP, a protein involved in HA degradation, were localized in the human epidermis, as well as in the dermis.
Topics: Extracellular Matrix; Humans; Hyaluronic Acid; Hyaluronoglucosaminidase; Proteins; Skin
PubMed: 35204753
DOI: 10.3390/biom12020251 -
Immunotherapy Sep 2017Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow... (Review)
Review
Most primary immunodeficiency diseases (PIDDs) resulting in antibody deficiency require intravenous or subcutaneous immunoglobulin G (SCIG) replacement therapy. The flow and distribution of SCIG to the vasculature is impeded by the glycosaminoglycan hyaluronan in the extracellular matrix, which limits the infusion rate and volume per site, necessitating frequent infusions and multiple infusion sites. Hyaluronidase depolymerizes hyaluronan and is a spreading factor for injectable biologics. Recombinant human hyaluronidase (rHuPH20) increases SCIG absorption and dispersion. In patients with PIDD, SCIG facilitated with rHuPH20 (IGHy) has been shown to prevent infections, be well-tolerated and reduce infusion frequency and number of infusion sites as compared with conventional SCIG. This article reviews IGHy clinical studies and real-world practice data in patients with PIDD.
Topics: Animals; Humans; Hyaluronoglucosaminidase; Immunoglobulins; Immunologic Deficiency Syndromes; Immunotherapy; Infusions, Subcutaneous; Practice Guidelines as Topic; Recombinant Proteins
PubMed: 28871852
DOI: 10.2217/imt-2017-0092 -
Medicine Nov 2022The gene cell migration inducing hyaluronidase 1 (CEMIP) is on chromosome 15q25 and codes for a 150-kDa protein with an N-terminal secretion signal, a G8 domain, 2 GG... (Review)
Review
The gene cell migration inducing hyaluronidase 1 (CEMIP) is on chromosome 15q25 and codes for a 150-kDa protein with an N-terminal secretion signal, a G8 domain, 2 GG domains, and several repeats. It was first described as a specific protein in the inner ear relating to nonsyndromic hearing loss. Recently, increasing research detected its association in various cancers, determining the progression, metastasis, and prognosis by influencing the proliferation and invasion of the cells. This relation is accomplished through various interacting pathways, such as the Wnt/β-catenin signaling pathway and the epidermal growth factor receptor signaling pathway. Thus, CEMIP could be a novel and potential focus for tumor diagnosis and treatment, but further studies on the regulatory role of CEMIP in vivo and in vitro are still needed. Herein, we summarize the process in recent studies of CEMIP, especially in cancer research.
Topics: Humans; Hyaluronoglucosaminidase; Wnt Signaling Pathway; Cell Movement
PubMed: 36451490
DOI: 10.1097/MD.0000000000031610