{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,16]],"date-time":"2026-04-16T09:31:47Z","timestamp":1776331907079,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Marie Sk\u0142odowska-Curie Actions (MSCA), called HORIZONMSCA-2021-SE-01","award":["101086322"],"award-info":[{"award-number":["101086322"]}]},{"name":"Marie Sk\u0142odowska-Curie Actions (MSCA), called HORIZONMSCA-2021-SE-01","award":["DBA.AD005.225"],"award-info":[{"award-number":["DBA.AD005.225"]}]},{"name":"Marie Sk\u0142odowska-Curie Actions (MSCA), called HORIZONMSCA-2021-SE-01","award":["B53C22001810006"],"award-info":[{"award-number":["B53C22001810006"]}]},{"name":"Marie Sk\u0142odowska-Curie Actions (MSCA), called HORIZONMSCA-2021-SE-01","award":["IR0000023"],"award-info":[{"award-number":["IR0000023"]}]},{"name":"CNR project FOE-2021","award":["101086322"],"award-info":[{"award-number":["101086322"]}]},{"name":"CNR project FOE-2021","award":["DBA.AD005.225"],"award-info":[{"award-number":["DBA.AD005.225"]}]},{"name":"CNR project FOE-2021","award":["B53C22001810006"],"award-info":[{"award-number":["B53C22001810006"]}]},{"name":"CNR project FOE-2021","award":["IR0000023"],"award-info":[{"award-number":["IR0000023"]}]},{"name":"SEELIFE (\u201cStrEngthEning the ItaLIan InFrastructure of Euro-bioimaging\u201d) of the European Union\u2014Next Generation EU PNRR MUR Infrastructure program","award":["101086322"],"award-info":[{"award-number":["101086322"]}]},{"name":"SEELIFE (\u201cStrEngthEning the ItaLIan InFrastructure of Euro-bioimaging\u201d) of the European Union\u2014Next Generation EU PNRR MUR Infrastructure program","award":["DBA.AD005.225"],"award-info":[{"award-number":["DBA.AD005.225"]}]},{"name":"SEELIFE (\u201cStrEngthEning the ItaLIan InFrastructure of Euro-bioimaging\u201d) of the European Union\u2014Next Generation EU PNRR MUR Infrastructure program","award":["B53C22001810006"],"award-info":[{"award-number":["B53C22001810006"]}]},{"name":"SEELIFE (\u201cStrEngthEning the ItaLIan InFrastructure of Euro-bioimaging\u201d) of the European Union\u2014Next Generation EU PNRR MUR Infrastructure program","award":["IR0000023"],"award-info":[{"award-number":["IR0000023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Aging is often a choice between developing cancer or autoimmune disorders, often due in part to loss of self-tolerance or loss of immunological recognition of rogue-acting tumor cells. Self-tolerance and cell recognition by the immune system are processes very much dependent on the specific signatures of glycans and glycosylated factors present on the cell plasma membrane or in the stromal components of tissue. Glycosylated factors are generated in nearly innumerable variations in nature, allowing for the immensely diverse role of these factors in aging and flexibility necessary for cellular interactions in tissue functionality. In previous studies, we showed that differential expression of TMEM230, an endoplasmic reticulum (ER) protein was associated with specific signatures of enzymes regulating glycan synthesis and processing and glycosylation in rheumatoid arthritis synovial tissue using single-cell transcript sequencing. In this current study, we characterize the genes and pathways co-modulated in all cell types of the synovial tissue with the enzymes regulating glycan synthesis and processing, as well as glycosylation. Genes and biological and molecular pathways associated with hallmarks of aging were in mitochondria-dependent oxidative phosphorylation and reactive oxygen species synthesis, ER-dependent stress and unfolded protein response, DNA repair (UV response and P53 signaling pathways), and senescence, glycolysis and apoptosis regulation through PI3K-AKT-mTOR signaling have been shown to play important roles in aging or neurodegeneration (such as Parkinson\u2019s and Alzheimer\u2019s disease). We propose that the downregulation of TMEM230 and RNASET2 may represent a paradigm for the study of age-dependent autoimmune disorders due to their role in regulating glycosylation, unfolded protein response, and PI3K-AKT-mTOR signaling.<\/jats:p>","DOI":"10.3390\/ijms26062412","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T12:22:52Z","timestamp":1741350172000},"page":"2412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Glycosylation Regulation by TMEM230 in Aging and Autoimmunity"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-1846","authenticated-orcid":false,"given":"Eleonora","family":"Piscitelli","sequence":"first","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edoardo","family":"Abeni","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristiana","family":"Balbino","sequence":"additional","affiliation":[{"name":"I.R.C.C.S. Ospedale Galeazzi-Sant Ambrogio, 20157 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4774-2223","authenticated-orcid":false,"given":"Elena","family":"Angeli","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Genoa, 16146 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cinzia","family":"Cocola","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5415-1515","authenticated-orcid":false,"given":"Paride","family":"Pelucchi","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mira","family":"Palizban","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4916-5928","authenticated-orcid":false,"given":"Alberto","family":"Diaspro","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Genoa, 16146 Genoa, Italy"},{"name":"Nanoscopy, Istituto Italiano Tecnologia, 16152 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2360-2496","authenticated-orcid":false,"given":"Martin","family":"G\u00f6tte","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, University Hospital of M\u00fcnster, 48149 M\u00fcnster, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ileana","family":"Zucchi","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"},{"name":"Associazione Fondazione Renato Dulbecco, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolland A.","family":"Reinbold","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Technologies, National Research Council, 20054 Segrate, Italy"},{"name":"Associazione Fondazione Renato Dulbecco, Via Fantoli 16\/15, 20138 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"ref_1","first-page":"427","article-title":"Rheumatoid arthritis: A review of the key clinical features and ongoing challenges of the disease","volume":"66","author":"Emery","year":"2024","journal-title":"Panminerva Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00281-022-00911-1","article-title":"Age as a risk factor in vasculitis","volume":"44","author":"Gloor","year":"2022","journal-title":"Semin. 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