Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome
Tenascin-X (TNX) is an extracellular matrix glycoprotein for which a deficiency results in a recessive form of classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder with hyperextensible skin without atrophic scarring, joint hypermobility, and easy bruising. Notably, p...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1107787/full |
| _version_ | 1797870578979307520 |
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| author | Emiko Okuda-Ashitaka Ken-ichi Matsumoto |
| author_facet | Emiko Okuda-Ashitaka Ken-ichi Matsumoto |
| author_sort | Emiko Okuda-Ashitaka |
| collection | DOAJ |
| description | Tenascin-X (TNX) is an extracellular matrix glycoprotein for which a deficiency results in a recessive form of classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder with hyperextensible skin without atrophic scarring, joint hypermobility, and easy bruising. Notably, patients with clEDS also suffer from not only chronic joint pain and chronic myalgia but also neurological abnormalities such as peripheral paresthesia and axonal polyneuropathy with high frequency. By using TNX-deficient (Tnxb−/−) mice, well-known as a model animal of clEDS, we recently showed that Tnxb−/− mice exhibit hypersensitivity to chemical stimuli and the development of mechanical allodynia due to the hypersensitization of myelinated A-fibers and activation of the spinal dorsal horn. Pain also occurs in other types of EDS. First, we review the underlying molecular mechanisms of pain in EDS, especially that in clEDS. In addition, the roles of TNX as a tumor suppressor protein in cancer progression have been reported. Recent in silico large-scale database analyses have shown that TNX is downregulated in various tumor tissues and that high expression of TNX in tumor cells has a good prognosis. We describe what is so far known about TNX as a tumor suppressor protein. Furthermore, some patients with clEDS show delayed wound healing. Tnxb−/− mice also exhibit impairment of epithelial wound healing in corneas. TNX is also involved in liver fibrosis. We address the molecular mechanism for the induction of COL1A1 by the expression of both a peptide derived from the fibrinogen-related domain of TNX and integrin α11. |
| first_indexed | 2024-04-10T00:30:43Z |
| format | Article |
| id | doaj.art-416239f7e5dc4fb29525c5ffb361a4f4 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T00:30:43Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-416239f7e5dc4fb29525c5ffb361a4f42023-03-15T04:21:19ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.11077871107787Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndromeEmiko Okuda-Ashitaka0Ken-ichi Matsumoto1Department of Biomedical Engineering, Osaka Institute of Technology, Osaka, JapanDepartment of Biosignaling and Radioisotope Experiment, Interdisciplinary Center for Science Research, Head Office for Research and Academic Information, Shimane University, Izumo, JapanTenascin-X (TNX) is an extracellular matrix glycoprotein for which a deficiency results in a recessive form of classical-like Ehlers-Danlos syndrome (clEDS), a heritable connective tissue disorder with hyperextensible skin without atrophic scarring, joint hypermobility, and easy bruising. Notably, patients with clEDS also suffer from not only chronic joint pain and chronic myalgia but also neurological abnormalities such as peripheral paresthesia and axonal polyneuropathy with high frequency. By using TNX-deficient (Tnxb−/−) mice, well-known as a model animal of clEDS, we recently showed that Tnxb−/− mice exhibit hypersensitivity to chemical stimuli and the development of mechanical allodynia due to the hypersensitization of myelinated A-fibers and activation of the spinal dorsal horn. Pain also occurs in other types of EDS. First, we review the underlying molecular mechanisms of pain in EDS, especially that in clEDS. In addition, the roles of TNX as a tumor suppressor protein in cancer progression have been reported. Recent in silico large-scale database analyses have shown that TNX is downregulated in various tumor tissues and that high expression of TNX in tumor cells has a good prognosis. We describe what is so far known about TNX as a tumor suppressor protein. Furthermore, some patients with clEDS show delayed wound healing. Tnxb−/− mice also exhibit impairment of epithelial wound healing in corneas. TNX is also involved in liver fibrosis. We address the molecular mechanism for the induction of COL1A1 by the expression of both a peptide derived from the fibrinogen-related domain of TNX and integrin α11.https://www.frontiersin.org/articles/10.3389/fgene.2023.1107787/fulltenascin-XEhlers-Danlos syndromesclEDSpaintumor suppressorfibrosis |
| spellingShingle | Emiko Okuda-Ashitaka Ken-ichi Matsumoto Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome Frontiers in Genetics tenascin-X Ehlers-Danlos syndromes clEDS pain tumor suppressor fibrosis |
| title | Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome |
| title_full | Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome |
| title_fullStr | Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome |
| title_full_unstemmed | Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome |
| title_short | Tenascin-X as a causal gene for classical-like Ehlers-Danlos syndrome |
| title_sort | tenascin x as a causal gene for classical like ehlers danlos syndrome |
| topic | tenascin-X Ehlers-Danlos syndromes clEDS pain tumor suppressor fibrosis |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1107787/full |
| work_keys_str_mv | AT emikookudaashitaka tenascinxasacausalgeneforclassicallikeehlersdanlossyndrome AT kenichimatsumoto tenascinxasacausalgeneforclassicallikeehlersdanlossyndrome |