{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:49:43Z","timestamp":1753890583984,"version":"3.41.2"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T00:00:00Z","timestamp":1610928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>The macrophage stimulating protein (MSP)\u2013Recepteur d\u2019origine nantais (RON) signaling pathway regulates macrophage function. Here, we verified RON receptor expression in bone marrow-derived dendritic cells (BMDCs) by real time-PCR, Western blot, and flow cytometry. Flow cytometry was used to detect the changes in MHC II and CD86 expression following the inhibition of RON in BMDCs and splenic\u00a0dendritic\u00a0cells (DCs). Immunoprecipitation and Western blot were used to detect the level of MHC II and CD86 ubiquitination. An enzyme-linked immunosorbent assay was used to detect cytokine release, and a mixed lymphocyte reaction was performed to evaluate DC maturity. The results show that the inhibition of RON leads to an increase in March-1 transcription, which intensifies the ubiquitination of MHC II and CD86 and ultimately leads to a decreased level of these two molecules. The mixed lymphocyte reaction provided evidence that RON inhibition decreased the ability of DCs to promote the proliferation of T cells. The MSP-RON signaling pathway may play an important role in lipopolysaccharide (LPS)-stimulated DC maturation through March-I and may protect DC differentiation following LPS stimulation.<\/jats:p>","DOI":"10.3389\/fcimb.2020.606340","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T05:51:45Z","timestamp":1610949105000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["RON Expression Mediates Lipopolysaccharide-Mediated Dendritic Cell Maturation via March-I"],"prefix":"10.3389","volume":"10","author":[{"given":"Lingtong","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xueling","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weifang","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hangping","family":"Yao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aai9338","article-title":"RON kinase: A target for treatment of cancer-induced bone destruction and osteoporosis","volume":"9","author":"Andrade","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"B2","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1189\/jlb.71.2.359","article-title":"Activation of the RON receptor tyrosine kinase protects murine macrophages from apoptotic death induced by bacterial lipopolysaccharide","volume":"71","author":"Chen","year":"2002","journal-title":"J. Leukoc Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"10449","DOI":"10.1073\/pnas.1507981112","article-title":"Ubiquitination by March-I prevents MHC class II recycling and promotes MHC class II turnover in antigen-presenting cells","volume":"112","author":"Cho","year":"2015","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B4","doi-asserted-by":"publisher","first-page":"20188","DOI":"10.1073\/pnas.1312994110","article-title":"Internalizing MHC class II-peptide complexes are ubiquitinated in early endosomes and targeted for lysosomal degradation","volume":"110","author":"Furuta","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2020.569082","article-title":"MSP-RON Pathway: Potential Regulator of Inflammation and Innate Immunity","volume":"11","author":"Huang","year":"2020","journal-title":"Front. Immunol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"787","DOI":"10.3324\/haematol.2017.180992","article-title":"RON kinase inhibition reduces renal endothelial injury in sickle cell disease mice","volume":"103","author":"Khaibullina","year":"2018","journal-title":"Haematologica"},{"key":"B7","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1189\/jlb.0210113","article-title":"Role of STK in mouse liver macrophage and endothelial cell responsiveness during acute endotoxemia","volume":"88","author":"Laskin","year":"2010","journal-title":"J. Leukoc Biol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1016\/j.bbrc.2013.03.108","article-title":"Macrophage-stimulating protein attenuates gentamicin-induced inflammation and apoptosis in human renal proximal tubular epithelial cells","volume":"434","author":"Lee","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B9","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1016\/j.ejphar.2013.05.006","article-title":"Macrophage-stimulating protein attenuates hydrogen peroxide-induced apoptosis in human renal HK-2 cells","volume":"715","author":"Lee","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"3904","DOI":"10.1074\/jbc.RA117.001322","article-title":"Ubiquitin-conjugating enzyme E2 D1 (Ube2D1) mediates lysine-independent ubiquitination of the E3 ubiquitin ligase March-I","volume":"293","author":"Lei","year":"2018","journal-title":"J. Biol. Chem."},{"key":"B11","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1038\/cmi.2016.58","article-title":"Cellular and molecular regulation of innate inflammatory responses","volume":"13","author":"Liu","year":"2016","journal-title":"Cell Mol. Immunol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"416","DOI":"10.1038\/ni.2015","article-title":"Intracellular MHC class II molecules promote TLR-triggered innate immune responses by maintaining activation of the kinase Btk","volume":"12","author":"Liu","year":"2011","journal-title":"Nat. Immunol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1046\/j.1523-1747.1998.00332.x","article-title":"Proteolytic cleavage and activation of pro-macrophage-stimulating protein and upregulation of its receptor in tissue injury","volume":"111","author":"Nanney","year":"1998","journal-title":"J. Invest. Dermatol."},{"key":"B14","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1111\/imr.12303","article-title":"Molecular mechanism and cellular function of MHCII ubiquitination","volume":"266","author":"Oh","year":"2015","journal-title":"Immunol. Rev."},{"key":"B15","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1038\/nri3771","article-title":"Dendritic cell metabolism","volume":"15","author":"Pearce","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1618","DOI":"10.1002\/hep.24239","article-title":"Ron receptor regulates Kupffer cell-dependent cytokine production and hepatocyte survival following endotoxin exposure in mice","volume":"53","author":"Stuart","year":"2011","journal-title":"Hepatology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1002\/path.2245","article-title":"Altered expression of the RON receptor tyrosine kinase in various epithelial cancers and its contribution to tumourigenic phenotypes in thyroid cancer cells","volume":"213","author":"Wang","year":"2007","journal-title":"J. Pathol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"2303","DOI":"10.4049\/jimmunol.181.4.2303","article-title":"The RON receptor tyrosine kinase regulates IFN-gamma production and responses in innate immunity","volume":"181","author":"Wilson","year":"2008","journal-title":"J. Immunol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"70","DOI":"10.4049\/jimmunol.177.1.70","article-title":"ERK and p38 MAPK signaling pathways negatively regulate CIITA gene expression in dendritic cells and macrophages","volume":"177","author":"Yao","year":"2006","journal-title":"J. Immunol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"686","DOI":"10.2174\/15680096113139990038","article-title":"Oncogenic Variant RON160 Expression in Breast Cancer and its Potential as a Therapeutic Target by Small Molecule Tyrosine Kinase Inhibitor","volume":"13","author":"Yao","year":"2013","journal-title":"Curr. Cancer Drug Targets"},{"key":"B21","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nrc3545","article-title":"MSP-RON signalling in cancer: pathogenesis and therapeutic potential","volume":"13","author":"Yao","year":"2013","journal-title":"Nat. Rev. Cancer"}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.606340\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,11]],"date-time":"2022-12-11T23:47:36Z","timestamp":1670802456000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2020.606340\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,18]]},"references-count":21,"alternative-id":["10.3389\/fcimb.2020.606340"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2020.606340","relation":{},"ISSN":["2235-2988"],"issn-type":[{"type":"electronic","value":"2235-2988"}],"subject":[],"published":{"date-parts":[[2021,1,18]]},"article-number":"606340"}}