{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T23:52:42Z","timestamp":1789170762333,"version":"build-2803163510"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The LONRF family of proteins consists of three isozymes, LONRF1\u20133, which harbors RING (really interesting new gene) domain and Lon substrate binding domain. We have recently identified LONRF2 as a protein quality control ubiquitin ligase that acts predominantly in neurons. LONRF2 selectively ubiquitylates misfolded or damaged proteins for degradation. LONRF2\u2212\/\u2212 mice exhibit late-onset neurological deficits. However, the physiological implications of other LONRF isozymes remain unclear. Here, we analysed Lonrf1 expression and transcriptomics at the single-cell level under normal and pathological conditions. We found that Lonrf1 was ubiquitously expressed in different tissues. Its expression in LSEC and Kupffer cells increased with age in the liver. Lonrf1high Kupffer cells showed activation of regulatory pathways of peptidase activity. In normal and NASH (nonalcoholic steatohepatitis) liver, Lonrf1high LSECs showed activation of NF-kB and p53 pathways and suppression of IFNa, IFNg and proteasome signalling independent of p16 expression. During wound healing, Lonrf1high\/p16low fibroblasts showed activation of cell growth and suppression of TGFb and BMP (bone morphogenetic protein) signalling, whereas Lonrf1high\/p16high fibroblasts showed activation of WNT (wingless and Int-1) signalling. These results suggest that although Lonrf1 does not seem to be associated with senescence induction and phenotypes, LONRF1 may play a key role in linking oxidative damage responses and tissue remodelling during wound healing in different modes in senescent and nonsenescent cells.<\/jats:p>","DOI":"10.1093\/jb\/mvad021","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T21:49:25Z","timestamp":1678312165000},"page":"459-469","source":"Crossref","is-referenced-by-count":11,"title":["Transcriptomic characterization of Lonrf1 at the single-cell level under pathophysiological conditions"],"prefix":"10.1093","volume":"173","author":[{"given":"Dan","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teh-Wei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-2618","authenticated-orcid":false,"given":"Sae","family":"Aratani","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"},{"name":"Graduate School of Medicine, Nippon Medical School Department of Endocrinology, Metabolism, and Nephrology, , 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satotaka","family":"Omori","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maho","family":"Tamatani","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshikazu","family":"Johmura","sequence":"additional","affiliation":[{"name":"Cancer Research Institute, Institute for Frontier Science Initiative, Kanazawa University Division of Cancer and Senescence Biology, , Kakuma-machi, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makoto","family":"Nakanishi","sequence":"additional","affiliation":[{"name":"Institute of Medical Science, University of Tokyo Division of Cancer Cell Biology, , 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"2023053106513278300_ref1","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1146\/annurev-biochem-060614-033955","article-title":"The biology of proteostasis in aging and disease","volume":"84","author":"Labbadia","year":"2015","journal-title":"Annu. 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Cell Biol."},{"key":"2023053106513278300_ref9","article-title":"Loss of LONRF2, a bona fide protein quality control ubiquitin-ligase, causes late-onset neurological deficits","author":"Li"},{"key":"2023053106513278300_ref10","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1016\/j.cmet.2020.09.006","article-title":"Generation of a p16 reporter mouse and its use to characterize and target p16(high) cells in vivo","volume":"32","author":"Omori","year":"2020","journal-title":"Cell Metab."},{"key":"2023053106513278300_ref11","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2023053106513278300_ref12","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"2023053106513278300_ref13","article-title":"Fast gene set enrichment analysis","author":"Gennady, Korotkevich","year":"2021","journal-title":"bioRxiv"},{"key":"2023053106513278300_ref14","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.molcel.2017.12.021","article-title":"Maintaining a healthy proteome during oxidative stress","volume":"69","author":"Reichmann","year":"2018","journal-title":"Mol. 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Gastroenterol."},{"key":"2023053106513278300_ref16","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/s41586-020-2496-1","article-title":"A single-cell transcriptomic atlas characterizes ageing tissues in the mouse","volume":"583","author":"Tabula Muris","year":"2020","journal-title":"Nature"},{"key":"2023053106513278300_ref17","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1002\/cphy.c120026","article-title":"Kupffer cells in the liver","volume":"3","author":"Dixon","year":"2013","journal-title":"Compr Physiol."},{"key":"2023053106513278300_ref18","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1016\/j.cmet.2008.04.003","article-title":"Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance","volume":"7","author":"Odegaard","year":"2008","journal-title":"Cell Metab."},{"key":"2023053106513278300_ref19","doi-asserted-by":"crossref","first-page":"44612","DOI":"10.1038\/srep44612","article-title":"Effect of modulation of PPAR-gamma activity on Kupffer cells M1\/M2 polarization in the development of non-alcoholic fatty liver disease","volume":"7","author":"Luo","year":"2017","journal-title":"Sci. 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