The role and regulation of TMEM2 (transmembrane protein 2) in HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization/ KIAA1199/CEMIP)-mediated HA depolymerization in human skin fibroblasts

Yoshino, Yuta; Goto, Masakazu; Hara, Hideaki; Inoue, Shintaro

doi:10.1016/j.bbrc.2018.09.097

Cited by 35 publications

(40 citation statements)

References 30 publications

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“…TMEM2 has been reported to act as a cell surface hyaluronidase in 293T cells (Yamamoto et al, 2017). However, we were unable to observe any HA-depolymerizing activity in cells transfected with TMEM2 (data not shown) in agreement with findings reported in skin cells (Yoshino, Goto, Hara, & Inoue, 2018). However, consistent with previous findings (Yoshida et al, 2013) live cultures of HEK293T cells expressing CEMIP digested HMW HA that was added to the cultures ( Figure 2c).…”

Section: Specific Modified Forms Of Apigenin Are Potent Hyaluronidasupporting

confidence: 92%

A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination

Matsumoto

Banine

et al. 2019

Glia

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Myelination delay and remyelination failure following insults to the central nervous system (CNS) impede axonal conduction and lead to motor, sensory and cognitive impairments. Both myelination and remyelination are often inhibited or delayed due to the failure of oligodendrocyte progenitor cells (OPCs) to mature into myelinating oligodendrocytes (OLs). Digestion products of the glycosaminoglycan hyaluronan (HA) have been implicated in blocking OPC maturation, but how these digestion products are generated is unclear. We tested the possibility that hyaluronidase activity is directly linked to the inhibition of OPC maturation by developing a novel modified flavonoid that functions as a hyaluronidase inhibitor. This compound, called S3, blocks some but not all hyaluronidases and only inhibits matrix metalloproteinase activity at high concentrations. We find that S3 reverses HA‐mediated inhibition of OPC maturation in vitro, an effect that can be overcome by excess recombinant hyaluronidase. Furthermore, we find that hyaluronidase inhibition by S3 accelerates OPC maturation in an in vitro model of perinatal white matter injury. Finally, blocking hyaluronidase activity with S3 promotes functional remyelination in mice with lysolecithin‐induced demyelinating corpus callosum lesions. All together, these findings support the notion that hyaluronidase activity originating from OPCs in CNS lesions is sufficient to prevent OPC maturation, which delays myelination or blocks remyelination. These data also indicate that modified flavonoids can act as selective inhibitors of hyaluronidase activity and can promote OPC maturation, making them excellent candidates to accelerate myelination or promote remyelination following perinatal and adult CNS insults.

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Section: Specific Modified Forms Of Apigenin Are Potent Hyaluronidasupporting

confidence: 92%

A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination

Matsumoto

Banine

et al. 2019

Glia

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“…Major clinical developmental phenotypes result from mutations in hyaluronidases such as mucopolysaccharidosis type IX from Hyal1 (Natowicz et al, 1996), bone defects, and cardiopulmonary dysfunction from loss of Hyal2 (Jadin et al, 2008;Chowdhury et al, 2013). Deafness and other abnormalities are associated with defects in HYBID Tang et al, 2019;Yoshida et al, 2013;Yoshino et al, 2017Yoshino et al, , 2018. Thus, as is frequently the case, this gene has several essential functions that extend beyond the immune defense role we have defined here.…”

Section: Discussionmentioning

confidence: 67%

“…These studies have not yet convincingly defined a primary cell type responsible for its synthesis but suggest that a fibroblast cell type may be the origin. Cemip has also been shown to be induced by histamine (Yoshino et al, 2018), and as histamine in skin is primarily released by mast cells, we examined if these cells could contribute to the response we observed. Mast cell-deficient mice had somewhat less Cemip but were still able to show increased expression after infection ( Figure S2).…”

Section: Discussionmentioning

confidence: 99%

“…Prior attempts to evaluate the function of previously defined mammalian hyaluronidases had not identified the gene responsible for mediating this critical event following infection of the skin. Cell migration-inducing protein (Cemip), alias HA-binding protein involved in HA depolymerization (HYBID) and KIAA1199, has been recently observed to have functional consequences in functions including deafness, bone growth, fibrosis, and tumor invasion Tang et al, 2019;Yoshida et al, 2013;Yoshino et al, 2017Yoshino et al, , 2018. In this study we hypothesized that Cemip may initiate HA breakdown during deep tissue infection by S. aureus and could be used to address the role of HA turnover in host defense.…”

Section: Introductionmentioning

confidence: 99%

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Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection

Dokoshi

Zhang

et al. 2020

Cell Reports

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“…CEMIP expression has been shown to lead to the degradation of extracellular HA in live cells [ 123 ]; however, its expression in the developing nervous system has yet to be fully elucidated. TMEM2 has also been shown to be involved in the digestion of extracellular HA [ 124 ], but its role as a hyaluronidase is currently debated, as another study has shown that the silencing of TMEM2 increases the degradation of HA [ 125 ]. These two proteins will need further study to identify their functions in the developing and adult nervous systems.…”

Section: Regulation Of Ha Catabolism In the Nervous Systemmentioning

confidence: 99%

Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System

Peters

Sherman

2020

IJMS

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Hyaluronic acid (HA) plays a vital role in the extracellular matrix of neural tissues. Originally thought to hydrate tissues and provide mechanical support, it is now clear that HA is also a complex signaling molecule that can regulate cell processes in the developing and adult nervous systems. Signaling properties are determined by molecular weight, bound proteins, and signal transduction through specific receptors. HA signaling regulates processes such as proliferation, differentiation, migration, and process extension in a variety of cell types including neural stem cells, neurons, astrocytes, microglia, and oligodendrocyte progenitors. The synthesis and catabolism of HA and the expression of HA receptors are altered in disease and influence neuroinflammation and disease pathogenesis. This review discusses the roles of HA, its synthesis and breakdown, as well as receptor expression in neurodevelopment, nervous system function and disease.

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The role and regulation of TMEM2 (transmembrane protein 2) in HYBID (hyaluronan (HA)-binding protein involved in HA depolymerization/ KIAA1199/CEMIP)-mediated HA depolymerization in human skin fibroblasts

Cited by 35 publications

References 30 publications

A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination

A modified flavonoid accelerates oligodendrocyte maturation and functional remyelination

Hyaluronan Degradation by Cemip Regulates Host Defense against Staphylococcus aureus Skin Infection

Diverse Roles for Hyaluronan and Hyaluronan Receptors in the Developing and Adult Nervous System

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